• Tuesday June 15, 2010, from 12.00 to 13.00
  Caetano Reis e Sousa, London Research Institute, Immunobiology Laboratory, London, United Kingdom 
  
  "Innate regulation of immunity by dendritic cells"

  Direct sensing of pathogen components is a major trigger of dendritic cell (DC) activation, leading to immunity. We have been studying multiple pattern-recognition pathways that mediate DC activation. One pathway for sensing infection by RNA viruses involves recognition of viral genomes or virally-infected cells in endosomal compartments and utilises members of the toll-like receptor (TLRs) family, including TLR9, 7, or 3. Viral genomes can additionally be recognised in the cytosol by DExD/H-box helicases such as RIG-I, which are activated by RNAs bearing 5' tri-phosphates. Finally, a distinct pathway involves cell surface and phagosomal recognition of fungi by C-type lectins, which signal via Syk kinase. Notably, some of these pathways are involved not only in direct sensing of pathogens but also in the recognition of self alterations that might accompany infection, such as induction of cell death. These studies help build a global picture of the receptors and signalling pathways that regulate DC activation and have applications in immunotherapy of cancer and infectious diseases.

  
  

  Tuesday June 8, 2010, from 12.00 to 13.00

  Aurore Dubois 

  "Regulation of Th2-type responses through CD8+ T lymphocytes in early life"

  Th2-biased immune responses characterizing neonates may influence the later onset of allergic disease. The contribution of regulatory T-cell populations in the prevention of Th2-driven pathologies in early life is poorly documented. We have investigated the potential of CD8⁺ T cells stimulated at birth with alloantigens to modulate the development of allergic airway inflammation. Newborn mice were immunized with semi-allogeneic dendritic cells (DC) and exposed at the adult stage to ovalbumin aeroallergens. DC immunized animals displayed a strong Th1 and Tc1/Tc2 alloantigen-specific response and were protected against the development of the allergic reaction. Adoptive transfers of CD8⁺ T cells from semi-allogeneic DC-immunized animals to adult b2m-deficient animals prevented the development of allergic response in particular IgE, IL-4 and IL-13 mRNA production in an IFN-g-dependent manner.

• Tuesday May 25, from 12.00 to 13.00
  Journal Club
  
  The following article was discussed : L Riol-Blanco et al, Immunological synapse formation inhibits, via NF-κB and FOXO1, the apoptosis of dendritic cells, Nature Immunol 10 : 753-760, 2009.
  It was presented by Nathalie Compte and Cédric Dewever. 
  
  
• Tuesday May 11, from 12.00 to 13.00
  Dominique Bron
  Institut Bordet, Hématologie, Brussels
  
  "Chronic lymphocytic leukemia : contributions and limits of biological prognostic factors"
  
  Clinical course of CLL patients is highly variable with overall survival ranging from a few months to more than 10 years. Reliable prognostic markers are of major importance both to identify subset of patients who do not necessitate any treatment and to clearly define patients with more aggressive disease who might benefit from each treatment. During the last decade, a plethora of new prognostic factors have been reported and correlated with survival or duration of response. This overview will discuss clinical, cytogenetical, biological and molecular markers and provide advantages of some of these. CLL research is a rapidly evolving area. Clinical trials taking into account some of these new prognostic factors are currently ongoing and could contribute to new guidelines in the management of CLL patients.

• Tuesday, April 27, from 12.00 to 13.00
  
  Seminar with David Vermijlen 
  
  "Antigen recognition by gammadelta T cells"
  
  For most gammadelta T cell subsets it is not known what their T cell receptor (TCR) recognizes, i.e. what the antigen or ligand is. After a general introduction on gammadelta T cells, David Vermijlen will focus on the well described interaction of a mouse gammadelta TCR with its ligand, the non-classical MHC class I molecule T22/T10. This interaction clearly differs from the recognition of classical MHC class I by alphabeta T cells. In this context, David Vermijlen will present as well recent data obtained at the Institute for Medical Immunology regarding the fetal gammadelta T cell response against CMV infection in utero. This includes the identification of a public germline-encoded anti-CMV gammadelta TCR.

• Tuesday, March 23, from 12.00 to 13.00
  
  Seminar with Anita van den Biggela, University of Western Australia, Telethon Institute for Child Health Research, Perth, Australia
  
  

  "Immune function and pneumococcal disease in young infants in Papua New Guinea"

  Streptococcus pneumoniae remains an important cause of serious morbidity and mortality in young infants in Papua New Guinea. This paper presents the results of a neonatal safety and immunogenicity pneumococcal conjugate vaccination trial in the ‘land of the unexpected' and discusses differences in neonatal immune function between children born against a high versus low background of microbial exposure that may influence vaccine competence and kinetics of postnatal immune development.    

• Tuesday, March 16, from 12.00 to 13.00
  
  Common seminar IBMM-IMI with David Zarkower, University of Minnesota, Department of Genetics, Cell Biology and Development, Minneapolis, USA
  
  

  "Doublesex-related transcription factors control testicular development and meiotic initiation in mammals"

  Genes containing the DM domain DNA binding motif are found throughout metazoans. They have been shown to control sex determination and sexual differentiation in several phyla, including insects, nematodes, and vertebrates, and thus are the most ancient sexual regulators discovered so far. Mammals have seven DM domain genes ("Dmrt genes") which control many aspects of development. This talk will focus mainly on the role of Dmrt1 in gonadal development in the mouse. To study Dmrt1 we have combined conditional gene targeting with genome-wide chromatin immunoprecipitation (ChIP) and gene expression profiling. This has revealed a surprising range of functions in germ cell and Sertoli cell differentiation and a surprisingly large number of target genes. Data will be presented indicating that DMRT1 serves as a "master regulator" to coordinate testis development and function and reproductive signaling.

• Tuesday, March 9, from 12.00 to 13.00
  
  Journal Club
  
  The following article was discussed : S. Quezada et al, Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts, J Exp Med doi10.1084jem.20091918.
  
• Tuesday, March 2, from 12.00 to 13.00 
  
  Common seminar IBMM-IMI with Alain Beschin
  
  VUB, VIB Department of molecular and cellular interactions, Brussels
  
  "Role of monocytic cell activation in liver inflammation : African trypanosome infection as a model"
   
  Although liver injury has many etiologies including viral and parasite infection, alcohol abuse, metabolic syndrome and autoimmune disorders, the cellular and pathogenic mechanisms resulting in organ inflammation seem relatively common and uniform. Recent studies demonstrate that this inflammation largely depends on recruitment of monocytes to the liver. Therefore, identifying the cellular pathways for monocyte subset recruitment, differentiation and maturation into tissue macrophages or DCs represent interesting novel targets for therapeutic intervention. In the recent years, we have used experimental infections with extracellular blood-borne African trypanosomes, which cause sleeping sickness in humans and Nagana disease in cattle in sub-Saharan Africa, as model systems to study infection-associated liver pathogenicity. The potential pathways governing the recruitment of inflammatory CD11b⁺Ly6C⁺ monocytic cells to the liver as well as their subsequent differentiation to functional pathogenic TNF and iNOS producing DCs during infection will be detailed the present talk.

• February 23 from 12.00 to 13.00
  
  Seminar with Hanspeter PIRCHER, University of Freiburg, Freiburg, Germany
  
  "The inhibitory NK receptor KLRG1: a nice marker but what is the function ?"
  
  

  The talk will focus on the inhibitory NK cell receptor KLRG1 (Killer cell Lectin-like Receptor G1) that is expressed in antigen-experienced T cells and NK cells. Viral and bacterial infections strongly induce KLRG1 expression and KLRG1 is widely used to identify T and NK cells that are approaching the end of their differentiation stage. Members of the classical cadherin family have been identified as ligands for KLRG1 and inhibition of lymphocyte function by interaction of KLRG1 with E-cadherin has been demonstrated. I will review the data on KLRG1 as a lymphocyte differentiation marker in men and mice and provide new structural and functional aspects of KLRG1/cadherin interactions. Beside KLRG1, I will also present experiments on the role of antibodies to prevent T cell exhaustion using lymphocytic choriomeningitis virus (LCMV) in mice and summarize our attempts in murine models to generate protective CD8 T cells using retroviral TCR gene transfer.

• February 9 from 12.00 to 13.00
  
  Seminar with Michael MACH, Universität Erlangen-Nürnberg, Erlangen, Germany
  
  "Protection from CMV infection by the humoral immune response"
  
  

  Human cytomegalovirus (HCMV) is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and infected newborns. The development of a vaccine for prevention of HCMV-related disease is considered a major goal. As with all successful vaccines, induction of potent antiviral antibodies will also be a prerequisite for an effective HCMV vaccine. However, the contribution of the humoral immune response to protection from HCMV disease is not known or even denied. We have used the murine CMV model to study the protective capacity of antiviral antibody. Our data clearly show that antiviral antibodies are perfectly capable of protecting immunosuppressed hosts from CMV disease and death. We are now exploring the mechanism of protection. One dominant antigen with respect to induction of antiviral antibodies is the glycoprotein gB, which is currently also used as vaccine in clinical trials. Interestingly, little is known about the humoral immune response to this antigen following natural infection and/or vaccination in humans. We have started to dissect the antibody repertoire against this protein following natural infection. This knowledge may be valuable in vaccine design.

• February 2 from 12.00 to 13.00
  
  Seminar with Emmanuelle Moens
  
  "IL-23R and TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells expressing high levels of cytotoxic mediators and producing IFN-γ and IL-17"
  
  The immune system in early life is regarded as immature. However, the IL-12 family member IL-23 is highly produced upon TLR stimulation by neonatal dendritic cells (DC). Human adult Vγ9Vδ2-T cells can be specifically stimulated via their TCR by phosphoantigens (like the pathogen-derived (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate, HMB-PP) or agents and infections that lead to their endogenous accumulation (like the aminobisphosphonate zoledronate). Since increasing evidence indicate that γδ T cells are important in early life, we investigated the effect of IL-23 on neonatal Vγ9Vδ2-T cells stimulated via their TCR. Zoledronate, but not HMB-PP, induced clear proliferation and IFN-γ production in neonatal Vγ9Vδ2-T cells. Addition of IL-23 to zoledronate co-stimulated the expression of IFN-γ and generated a distinct IFN-γ-negative neonatal Vγ9Vδ2-T cell population producing IL-17. Furthermore, IL-23 co-stimulated significantly the expression of a range of cytotoxic mediators (perforin, granzymes, granulysin). While the co-stimulatory effect of IL-23 on IFN-γ and cytotoxic mediators was also observed within adult Vγ9Vδ2-T cells, the induction of IL-17 was a unique property of neonatal Vγ9Vδ2-T cells. In conclusion, neonatal DC-derived IL-23 combined with specific TCR signaling drives the generation of neonatal Vγ9Vδ2-T cells equipped with a range of cytotoxic mediators and distinct subpopulations producing IFN-γ and IL-17.

• Tuesday January 5, from 12.00 to 13.00
  
  Journal Club
  
  The following article was discussed :
  P. Ebert et al, An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a, Nature Immunol 2009 ; 10 : 1162-1170.
  
  

• Tuesday, December 8, from 12.00 to 13.00
  
  Seminar with Emmanuelle VIRE
  University of Cambridge, Gurdon Institute, Cambridge, United Kingdom
  
  

  "Epigenetics in human cancer : 2 shorts stories about mechanisms"
  
  

  Epigenetics encompasses changes in gene expression profiles that occur without alterations to the genomic DNA sequence of a cell. This arises from the modifications of the chromatin, a structure made from the wrapping of DNA around histone proteins. Modifications of chromatin occur both at the DNA and histone levels leading to crucial changes in the regulation of gene expression. Therefore epigenetics play a key role in many biological processes such as cell development, differenciation and function as well as in cancer. Our results highlight a previously unrecognized direct connection between two key epigenetic repression systems : Polycomb Group (PcG) proteins and DNA methylation. Further, we recently identify EMSY as a novel regulator of gene expression and provide new insight into the function of EMSY in sporadic breast cancer.

• Tuesday, December 15, from 12.00 to 13.00 at the Auditorium Albert Claude, Point Centre
  (this seminar will be followed by a lunch from 13.00 to 14.00)
  
  Common seminar IBMM-IMI with Jean-Christophe MARINE
  University of Ghent, VIB Laboratory for Molecular Cancer Biology, Ghent
  
  "MicroRNA-processing and Tumorigenesis"
  
  MicroRNAs (miRs) are non-coding RNAs that regulate gene expression by targeting messenger RNAs for translational repression and/or degradation. It has become apparent that miRs and molecules involved in their biogenesis contribute to tumorigenesis. Overall down-regulation of miR levels in cancer has been reported and this down-regulation, likely to be at least partly a consequence of aberrant processing of their precursor transcripts, appears to contribute significantly to the progression of the disease. To further study the role of the miR-processing machinery in cancer development, Dicer function has been genetically ablated in a mouse model of retinoblastoma (Chx10-cre;Rblox/lox; p107-/-). Our data suggest that Dicer functions as a haplo-insufficient tumor suppressor gene in retinoblastoma at least partly by compromising p53 tumor suppressor function.
  

• Tuesday, November 3, from 12.00 to 13.00
  
  Seminar with Gérard EBERL
  Institut Pasteur, Lymphoid Tissue Development Unit, Paris, France
  
  "Microbiota and the development of the intestinal immune system"
  
  After birth, lymphoid tissue inducer (LTi)-like cells are clustered as cryptopatches in the intestinal lamina propria. Cryptopatches are sensors of the bacterial flora and induce the formation of isolated lymphoid follicles (ILFs) through the recruitment of naïve B cells. We have found that peptidoglycans shed by Gram-negative bacteria are recognized by the innate receptor NOD1 in epithelial cells, which then induce the production of the chemokine CCL20 and the b defensin-3, and the activation of LTi-like cells and B cells through CCR6. This mechanism of bacteria-induced lymphoid tissue formation culminates in the production of IgA that target the very same bacterial community, thereby establishing a negative feedback loop and a mechanism for intestinal homeostasis. The equilibrium between the commensal community and the immune system is critical for digestion and defense against pathogens, therefore the different cellular and molecular components ruling this equilibrium are under intense investigation. We now identify the type of microbes that manipulate the immune system, in particular lymphoid tissues, and the impact of the immune system on the microbial community.  
  
    
• Tuesday, November 10, from 12.00 to 13.00
  
  Seminar with Christelle LANGLET
  Centre d'Immunologie de Marseille Luminy, France
  
  "Molecular and cellular pathways responsible for the Th2 lymphoproliferative disorder afflicting mice with disabled LAT adaptor"
  
  Linker for Activation of T cells (LAT) is an adaptor that becomes activated following TCR engagement. It is essential to mediate activation of downstream signaling effectors. Mutant mice where tyrosine 136 of LAT was replaced with a phenylalanine (Lat^Y136F mice) develop a lymphoproliferative disorder involving polyclonal CD4 effector T cells that produce massive amounts of IL-4 and trigger severe Th2 inflammation. This uncontrolled proliferation seems to be independent of MHCII-TLR interaction. In the present study, we investigate the mechanisms responsible for the development of such a lymphoproliferative disease and compare them to what occurs in normal T cells.
  
  
  
• Tuesday, November 17, from 12.00 to 13.00
  
  Seminar with Laurent BAUD
  Hôpital Tenon, Physiology, Paris, France
  
  "Calpains : a double edged sword in ischemia, inflammation, and fibrosis"
  
  Calpains are calcium-activated neutral cysteine proteases, which are ubiquitously expressed. They play potentially a role in inflammation, as they are involved in NF-kB-dependent expression of pro-inflammatory cytokines, in inflammatory mediator processing, in inflammatory cell chemotaxis, and in cleavage of HSP 90, which is required to maintain binding and anti-inflammatory efficacy of glucocorticoid. Calpain activity is tightly controlled by calpastatin, a specific endogenous inhibitor. Thus, to identify precisely calpain roles in inflammation, we created mice transgenic for calpastatin. Using this original tool, we ascertained the functions of calpains in models of glomerulonephritis, hypertension, and transplantation.
  Interestingly, calpains are externalized during inflammatory process. Using in vitro and in vivo approaches, we found that externalized calpains play a paradoxical role in limiting inflammatory reaction and promoting tissue repair. It will be of interest to focus on novel anti-inflammatory drugs that increase calpain secretion, as this strategy would decrease the availability of intracellular calpains (pro-inflammatory) and increase that of extracellular calpains (anti-inflammatory). Meanwhile ongoing studies aim at identifying molecular mechanisms of calpain secretion.
  
  
• Tuesday, November 24, from 12.00 to 13.00
  
  Seminar with Vijay MORAMPUDI
  Scientific Institute of Public Health, Toxoplasma Research Unit, Brussels
  
  

  "The capacity to modulate innate immunity of intestinal epithelium discriminates high and low virulence in Toxoplasma gondii infections"

  The mucosal surfaces of the gastrointestinal tract are in direct contact with the external environment and are therefore susceptible to invasion by pathogens. The intestinal epithelial cell (IEC) layer previously known for its physiological adaptations to act as a barrier between the intestinal lumen and host connective tissue is now also known to initiate and regulate immune cell function. Toxoplasma gondii, a disease causing protozoan parasite is acquired via the gastrointestinal route and encounters IEC as an early host. The population structure of T. gondii is highly clonal; however clinical isolates are divided into three genotypes having less than 2% genomic difference but distinct virulence. Our study provides evidence for the distinct capacity of high and low virulent T. gondii to modulate innate immune responses of intestinal epithelial cells.

• Tuesday, October 20, from 12.00 to 13.00
  
  Seminar with Guillaume OLDENHOVE de GUERTECHIN
  Animal Physiology, IBMM, ULB
  
  

  "Th1 environment induces collapse and acquisition of effector phenotype by Foxp3+Treg during lethal intestinal infection"

  In the present study, using a model of lethal oral infection with Toxoplasma gondii, we examined the fate of both induced and natural Treg in the face of strong inflammatory responses occurring in a tolerogenic?prone environment. We found that during highly Th1-polarized mucosal immune responses, Treg populations collapse via multiple pathways including blockade of Treg induction and disruption of endogenous Treg homeostasis. In particular, shutdown of IL-2 in the highly Th1-polarized environment triggered by infection directly contributes to Treg incapacity to parallel effector responses and eventually leads to immunopathogenesis. Furthermore, we found that environmental cues provided by both local dendritic cells and effector T cells can superimpose T-bet and IFN-γ expression by Treg. These data reveal a novel mechanism for Th1 pathogenicity that extends beyond their proinflammatory program to limit Treg survival.

• Tuesday, October 27, from 12.00 to 13.00
  
  Seminar with François VAN LAETHEM
  Expérimental immunology, National Institutes of Health, Bethesda, USA
  
  

  "Basis for selection of MHC-independent alpha-beta T Cells in the thymus"

  The thymus generates MHC-restricted abT cells that only recognize antigenic ligands in association with MHC or MHC-like molecules.  We have recently reported that MHC-independent abT cells can be generated in mice deficient in both coreceptors as well as MHC, called ‘Quad-deficient' mice, and that such mice contained a diverse abT cell repertoire whose MHC-independence was confirmed at the clonal level.  We now show that signaling and selection of these MHC-independent T cells required the presence of TCR as Quad-/- thymocytes deficient in TCRa and pTa expression were not signaled nor selected.  Furthermore, we were able to confer the MHC-independent specificity of individual T cell hybridomas by retrovirally introducing both TCRa and TCRb chains in a TCR negative cell line.  The critical effect of the Lck sequestration by coreceptors was examined by introducing CD4 transgenes into Quad-deficient mice.  Whereas sequestration of Lck by wild-type CD4 blocked signaling by non-MHC ligands on ab thymocytes, introducing a tailless form of CD4 didn't.  Finally, we generated Lck transgenes that cannot interact with CD4 and CD8 coreceptors and we were able to generate MHC independent abT cells. We conclude that in the absence of Lck sequestration by coreceptors, thymocytes can be signaled by non-MHC ligands.  Collectively these data demonstrate that CD4 and CD8 coreceptors impose MHC-specificity on a broad abTCR repertoire by preventing thymocytes to be selected by non-MHC ligands.

• Tuesday September 22, from 12.00 to 13.00
  
  Seminar with Julie DECHANET-MERVILLE
  Université de Bordeaux, CNRS 5164, Bordeaux, France
  
  "Multiple facets of gamma-delta T cells in organ transplantation"
  
  

  Since our original observation of a conspicuous expansion of gamma-delta T cells in the blood of organ transplant recipients during Cytomegalovirus (CMV) infections, we are trying to understand the way of action of this gamma-delta T cell subset usually located in tissues. We have shown that some of these gamma-delta T cell clones display dual TCR-dependent killing activity toward carcinoma and toward CMV-infected cells. This unique model gives us a chance to answer key questions regarding gamma-delta T cell biology. We showed that these unconventional T cells strikingky behave akin to CD8+ alpha-beta T cells with respect to their expansion kinetics in blood, their phenotype and their ability to generate an adaptive immune response. However, one specificity of CMV-induced gamma-delta T cells is their expression of CD16 (FcgRIIIa) which provide them with the ability to secrete important amounts of IFNg through recognition of immune complexes. We also unveiled an association between a high percentage of CMV-induced gamma-delta T cells and a reduced cancer risk in kidney recipients and demonstrated the capacity of gamma-delta T cell clones to inhibit the growth of human tumor xenograft in immunodeficient mice. Altogether our results strongly suggest the protective role held by this gamma-delta T lymphocyte subset in the host response to CMV and in tumor surveillance. They provide basis to suggest the manipulation of these cells or their activating ligands for therapeutic targeting of human malignancies or viral infections.
  

• Friday September 25, from 12.00 to 13.00 at the Auditorium Albert Claude, Point Centre
  (this seminar will be followed by a lunch from 13.00 to 14.00)
  
  Common seminar IBMM-IMI with Carolina BARRILLAS-MURY
  National Institute of Allergy and Infectious Diseases, Bethesda, USA
  
  "Plasmodium-mosquito interactions : a story of insect immune memory and parasite immune evasion"
  
  

  Insects rely on the innate immune system to defend themselves from pathogens, and are thought to be incapable of mounting adaptive immune response. We investigated whether pre-exposure of adult females to Plasmodium infection could enhance their ability to respond to a second infection. We found adult mosquito females challenged with Plasmodium are able to "learn" and respond more efficiently to subsequent challenges. Preliminary data indicate that the priming response involves hemocyte differentiation. We identified a single QTL in Chr. 13 that confers an African strain of Plasmodium falciparum (GB4) the ability to evade the immune response of An. gambiae (L35) females. In contrast, 98-100% of P. falciparum 7G8 parasites (Brazilian strain) are detected by the mosquito immune system and killed.  The location of the recombination sites flanking the central marker in the QTL was determined by saturating this region with additional microsatellite markers and defines a 171.8 kb region coding for 42 genes. Several complementary strategies to narrow down this region and identify the gene(s) that allow African strains of P. falciparum to evade the immune system and infect mosquitoes will be discussed.

• Tuesday June 23, from 12.00 to 13.00 at the Auditorium Albert Claude, Point Centre
  (this seminar will be followed by a lunch from 13.00 to 14.00)
  
  Common Seminar IBMM-IMI with Pierre VAN DER BRUGGEN
  Ludwig Institute for Cancer Research, UCL, Bruxelles
  
  "Is it possible to correct the anergy of human tumor-infiltrating lymphocytes ? "
  
  We have recently discovered a new type of anergy of human CD8 T cells, which is observed on tumor-infiltrating lymphocytes. Tumor-infiltrating lymphocytes were anergic, being unable to secrete IFN-gamma or other cytokines after stimulation with anti-CD3/CD28 antibodies. TCR were observed to be distant from CD8 on the cell surface of tumor-infiltrating lymphocytes, whereas TCR and CD8 co-localized on blood T lymphocytes. We hypothesized that the absence of TCR-CD8 co-localization at the cell surface of anergic T cells is due to the loss of mobility of the TCR, which is trapped in a lattice of galectin-3. Surface glycoproteins, including the TCR, can be heavily N-glycosylated and interact with extracellular galectin-3. Galectin-3 is frequently released by tumor cells, can form homopentamers and therefore create a glycoprotein-galectin lattice. To test this hypothesis, tumor-infiltrating lymphocytes were incubated with N-acetyllactosamine, a disaccharide ligand of galectin-3. This treatment restored the TCR-CD8 co-localization and the capacity to secrete IFN-gamma and other cytokines after stimulation. These observations indicate that ex vivo human tumor-infiltrating lymphocytes can recover their effector functions with galectin ligands and suggest that treatment of cancer patients with galectin ligands could correct the anergy of tumor-infiltrating lymphocytes. Further reading Demotte, N, et al. Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes. Immunity 28:414-24, 2008.  
  
  
• Tuesday June 16, from 12.00 to 13.00 at the Auditorium Albert Claude, Point Centre
  (this seminar will be followed by a lunch from 13.00 to 14.00)
  
  Common Seminar IBMM-IMI with Anna Maria MARINI
  Physiology Moleculaire de la Cellule, ULB, Gosselies
  
  "From yeast ammonium transport proteins to human Rhesus factors"
  
  Ammonium is a principal nitrogen source for microorganisms and plants, whereas in animals it is a metabolic product best known for its cytotoxic effects. Ammonium handling is also critical for systemic pH regulation, renal ammonium production and excretion being essential for net acid elimination. Although specific ammonium transport systems might play important roles in all domains of life, the study of such proteins has been hampered by a lack of molecular characterisation. In 1994, using the yeast Saccharomyces cerevisiae as a model, we cloned the first gene encoding an ammonium transport protein which defined a widely conserved family. We next found that the Rhesus factors, including the human antigens from the Rhesus blood group, belong to this novel family. More recently, by targeting the Rhcg gene in mouse, we showed that the corresponding Rhesus protein is required for urinary ammonium excretion and for the regulation of acid-base homeostasis.

• Tuesday 26 May 2009, from 12.00 to 13.00
  Stanislas GORIELY
  
  "Ontogeny of human dendritic cell responses in the first year of life"
   

• Tuesday 19 May 2009,  from 12.00 to 13.00
  Ligia CRACIUN

'Homeostatic proliferation of memory type CD8⁺ T cells as a barrier to tolerance induction in a clinical protocol of liver transplantation'

Background : Peritransplant T cell depletion was suggested to favour tolerance induction in solid organ transplantation. In a pilot trial in liver transplantation (LT), we performed a set of assays for the monitoring of patients included in protocols aiming the minimisation of immunosuppression to induce graft tolerance.

Methods : Peripheral blood was obtained from 16 patients received immunodepleting regimen followed by IS withdrawal at preTx, 2, 4, 6 and 12 months postTx. In these patients, we characterized the phenotype of circulating lymphocytes, we monitored interleukin (IL)-7 serum levels, interferon (IFN)- g and IL-17 mRNA accumulation in mixed leucocyte reaction (MLR) and intra-graft IFN-g mRNA and IL-17 expression by qPCR and immunohistochemistry respectively.

Results : Ten patients were included. In all cases, ATG therapy induced a profound early CD4⁺ and CD8⁺ T cells depletion. CD4⁺ T cells remained low for more than 12 months, but, in contrast, CD8⁺ T cells, mostly of memory phenotype (T_EMRA, CCR7^-CD45RA⁺), recovered from month 2, reaching levels above pretransplant counts at month 6. After ATG administration, increased IL-7 serum levels were measured, peaking at day 25 and remaining elevated until day 300. In the first 3 patients, attempts of IS discontinuation at days 140, 206 and 124 was followed by reversible acute rejection (AR), 140, 40 and 39 after IS withdrawal. At the time of AR, significant levels of IFN- g and IL-17 mRNA were measured in MLR between recipient T-cells and donor spleen cells. Consistently, high levels of IFN- g mRNA and IL-17 were measured within rejecting liver grafts.

Conclusions : Lymphopenia-induced IL-7 production following ATG induction might lead to homeostatic proliferation of memory-type CD8⁺ T-cells, potentially responsible for AR after IS withdrawal through IFN- g and IL-17 secretion.

• Tuesday 12 May 2009, from 12.00 to 13.00
  Celine MOLLE
  

  "Differential involvement of IRF members in IL-27 synthesis induced by TLR ligation"

  Interleukin (IL)-27, a member of the IL-12 family, is a heterodimeric cytokine composed of Epstein-Barr virus-induced gene 3 (EBI3) and p28. Produced by dendritic cells (DCs) in response to Toll-like receptor (TLR) ligands, IL-27 recently emerged as a key regulatory cytokine of inflammatory responses. We focused on the molecular pathways implicated in TLR induced IL-27 expression. In a previous work, we demonstrated that interferon regulatory factor (IRF) 3, activated downstream of TRIF, acts as a master switch for IL-27p28 synthesis by LPS-stimulated DCs. Herein, we further explored the role of other members of the IRF family in IL-27 production in response to TLR agonists, type I and type II interferons (IFN). We first observed that type I IFN signaling was required for p28 expression downstream of TLR3 and TLR4. Using DC derived from knock-out mice, we then assessed the role of different IRF members in the regulation of IL-27. The positive role of IRF9 and IRF1 was confirmed in electrophoretic mobility shift assays and reporter gene experiments. We found that the different IRF members activated synergistically the IL-27p28 promoter. Finally, we assessed the role of these transcription factors in IL-27 expression in vivo upon injection of TLR ligands in knock-out mice. Taken together, our results indicate that IRF members are differentially implicated in the regulation of IL-27p28 gene synthesis.

• Tuesday May 5, 2009 from 12.00 to 13.00
  Guy CORNELIS
  Focal Area: Infection Biology, Biozentrum, Universität Basel, Basel, Switzerland

"The injectisome, a complex bacterial nanomachine for cellular sabotage"

The type III secretion injectisome is a nanosyringe that injects bacterial effector proteins straight into the cytosol of eukaryotic cells. The effectors interfere with intracellular signaling processes. The injectisome is evolutionary related to the flagellum, with which it shares structural and functional similarities.  It consists of a basal body made of several rings spanning the bacterial membranes, connected by a central tube.  The lower ring contains an ATPase related to the F0 and the vacuolar ATPase.  On top of the basal body, comes a short stiff needle terminated with a tip structure.  The basal body is assembled sequentially by the Sec pathway. As soon as the export apparatus itself is assembled, it takes over the assembly process and exports the needle subunits (early substrates).  Needle elongation is controlled by YscP, acting as a molecular ruler or a timer, released at the end of the process. YscP seems to be partially folded and its total length approximates the length of the needle plus the basal body, supporting the ruler model. When assembly of the needle is complete, the C-terminal domain of YscP interacts with the export apparatus and changes the substrate specificity, which becomes ready to export the needle tip protein, then pore formers and finally effectors. One protein from the export apparatus specifically recognizes the various classes of export substrates.

• Tuesday 14 April 2009, from 12.00 to 13.00
  Seminar with
  Frederic LHOMME
  

"ImageStream : a new technology with high potential"

ImageStream allows to capture pictures of single cells in flow and  provides statistics related on the intensity of markers (as in flow cytometry) but also morphology and marker localization of cell populations. Its main interest lies in the possibility to correlate results coming from microscopy and flow cytometry in order to generate qualitative and quantitative cell profiles. From a purely microscopy point of view, ImageStream makes possible the visual acquisition of cells in flow, decreases time acquisition compared to traditional microscopy and allows to generate cell population statistics. As regards flow cytometry, morphological parameters of cells normally determined by microscopy ideally complete those gained by flow cytometry. ImageStream also enables to measure the quantity, the position and the motion of molecules on, in or between cells. It furthermore measures the position and the colocalisation of multiple markers and morphologically quantifies distinct cell subpopulations.

Numerous applications are already reported such as:

•        Apoptosis / necrosis

•        Cell classification

•        Marker colocalisation

•        NFkB translocation

•        Marker cap quatification

•        Molecular trafficking

•        TUNEL Apoptosis

•        Hematology

•        Aspect ratio for cellular morphology

•        Pseudopod formation and polarization

•        Bacterial analysis

•        Phagocytosis

•        T cell / APC conjugates

•        High throughput FISH-IS

•       Infectious disease

•        Cell cycle and mitosis

• Tuesday 24 March 2009, from 12.00 to 13.00
  
  Stephane TEMMERMAN
  "The inflamasome: a key target of vaccine adjuvants

• Tuesday 10 February, 2009 - 12.00 to 13.00

Magali NOVAL RIVAS
Agressive graft-versus-host disease induced by PD-L1 blockade

• Tuesday February 3, 2009, 12.00 to 13.00

Amandine LEGAT
Role of CD14 in IRF3-dependent TLR4-mediated responses

• Tuesday January 27,2009, 12.00 to 14.00 PM

• Tuesday Januray 20, 2009, 12.00 to 13.00 PM
  
  B.VOKAER and L.M. CHARBONNIER
  Implication of IL-17 in allograft rejection 
  
  
• Tuesday Januray 13, 2009, 12.00 to 13.00 PM
  
  Aurore DUBOIS
  Regulation of allergy through bystander stimulation of CD8⁺ T lymphocytes in early life
  
  
• Tuesday Januray 6, 2009, 12.00 to 13.00 PM

Ken FIELD
Buckwell University, Lewisburg, Pennsylvania, USA
Immunomodulation by Farnesyltransferase Inhibirtors

• Tuesday December 2, 2008, 12.00 to 13.00 PM
  
  Common seminar IBMM-IMI
  Thomas WEICHHART
  Clinical Division of Nephrology and Dialysis, Medical University of Vienne, Austria
  Rapamycin and mTor inhibitors: more than immunosuppressors
  Auditorium Albert Claude, Point Centre
  
  
• Tuesday December 9, 2008, 12.00 to 13.00 PM
  
  Laure YSEBRANT DE LENDONCK
  IL-27 in neonatal immunity
  
  
• Tuesday December 16, 2008, 12.00 to 13.00 PM
  
  Thomas WEKERLE
  Department of Surgery,Division of Transplantation, Vienna General Hospital, Austria
  Transplantation tolerance through mixed chimerism: Progress and Challenge
  
  
• Tuesday December 23, 2008, 12.00 to 13.00 PM
  
  Patrick STORDEUR and Mathieu VOKAER
  Multiple sclerosis: new biomarkers of the disease activity and response to the IFN-beta therapy
  

• Tuesday November 4, 2008, 12.00 to 13.00 PM
  
  Common Seminar IBMM-IMI
  Tony LAHOUTTE
  Department of Nuclear Medicine, UZ Brussel, Vrije Universiteit Brussel
  Multi-modality small animal imaging in biomedical research
  Auditorium Albert Claude, Point Centre
  
  
• Wednesday November 12, 2008, 12.00 to 13.00 PM
  
  Common Seminar IBMM-IMI
  Markus ENGSTLER
  Institute of Microbiology and Genetics, Darmstadt University of Technology, Germany
  Outswimming antibody attack? The role of nanoscale hydrodynamics in immune invasion
  Auditorium Albert Claude, Point Centre
  
  
• Tuesday November 18, 2008, 12.00 to 13.00 PM
  
  Isabelle DEBOCK
  Inhibition of Th2 skewed response in neonate promotes the development of Th17 type effector cells
  
  
• Tuesday November 25, 2008, 12.00 to 13.00 PM
  
  Emmanuelle MOENS
  Human gammadelta T cells as targets for novel adjuvants in early life
  

• Tuesday October 14, 2008, 12.00 to 13.00 PM
  
  Brigitte ADAMS
  Role of CD8 T cells in the regulation of TH2 pathology in early life
  
  
• Tuesday October 21, 2008, 12.00 to 13.00 PM
  
  Common Seminar IBMM-IMI
  Bart LAMBRECHT
  Department of Internal Medicine, University of Ghent
  The danger within : role of endogenous danger signals in DC function and asthma
  Auditorium Point Centre
  
  
• Tuesday October 28, 2008, 12.00 to 13.00 PM
  
  Nicolas Twité
  Immune mechanisms involved in the control of human cytomegalovirus replication in epithelial cells

• Tuesday September 2, 2008, 12.00 to 13.00 PM
  
  Francesco ANNUNZIATO (Department of Internal Medicine, Florence University, Italy)
  Human interleukin-17-producing cells: origin, phenotype and functional features
  
  
• Tuesday September 9, 2008, 12.00 to 13.00 PM
  
  Benoit VANHOLLEBEKE (Institute for Molecular Biology and Medicine, ULB)
  A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans
  
  
• Tuesday September 16, 2008, 12.00 to 13.00 PM
  
  Common seminar IBMM-IMI
  Cédric BLANPAIN (Interdisciplinary Research Institute, ULB)
  Multipotent cardiovascular progenitors: from basic research to therapeutic applications
  Auditorium Point Centre
  
  
• Tuesday September 23, 2008, 12.00 to 13.00 PM
  
  Patrizia LOI
  IRF3 deficiency enhances liver ischemia-reperfusion injury
  
  
• Tuesday September 30, 2008, 12.00 to 13.00 PM
  
  François MAHIEU
  Innate immune responses in newborn mice

• Monday June 2, 2008, 12.00 to 13.00 PM
  
  Delphine GOUX (Associate Editor, European Journal of Immunology)
  Publishing in Immunology :The Editor's vision
  
  
• Tuesday June 10, 2008, 12.00 to 13.00 PM
  
  Olivier THAUNAT (Département de Transplantation et d'Immunologie Clinique, Hôpital Edouard Herriot, Lyon)
  Lymphoid neogenesis during chronic rejection : evidence for a local alloimune response
  
  
• Tuesday June 17, 2008, 12.00 to 13.00 PM
  
  René VAN LIER (Department of Experimental Immunology, Academic Medical Center, University of Amsterdam)
  Molecular basis of CD8+ T cell differentiation
  
  
• Tuesday June 24, 2008, 12.00 to 13.00 PM
  
  Christelle LANGLET
  Role of protein kinase C alpha in MYD88-dependent TLR signalling pathways
  
  
• Monday June 30, 2008, 12.00 to 13.00 PM
  
  David TORRES (Inserm U774, "Biomolécules et Inflammation pulmonaire", Institut Pasteur, Lille)
  Asthma exacerbation induced by the synthetic analog of viral dsRNA administration in the airways: implication of airway epithelium and dendritic cells

• Tuesday May 6, 2008, 12.00 to 13.00
  
  Common seminar IBMM-IMI
  Jean-François DUBREMETZ (UMR5539 Centre National de la Recherche Scientifique, Université de Montpellier 2)
  How Toxoplasma gondii harnesses its host cell
  Auditorium Point Centre
  
  
• Tuesday May 13, 2008, 12.00 to 13.00
  
  Laurent MERIC DE BELLEFON
  Immunological exploration of a chronic inflammatory disease in a patient exposed to toxics
  
  
• Tuesday May 20, 12.00 to 13.00
  
  Lionel POULIN (Centre d'Immunologie de Marseille-Luminy)
  Identification of a novel population of Langerine-positive dendritic cells
  
  
• Tuesday May 27, 2008, 12.00 to 13.00
  
  Dominique DE WIT
  TLR4 ligands and dendritic cells

• Tuesday April 8, 2008, 12.00 to 13.00 PM
  
  Common seminar IBMM-IMI
  Sophie LUCAS (Institute for Cancer Research)
  Human Treg clones as tools to study the biology of regulatory T lymphocytes
  Auditorium Point centre

• Tuesday April 15, 2008, 12.00 to 13.00 PM
  
  Virginie DE WILDE
  Dampening of alloimmunity by Toll-Like receptor 4 desensitization
  
  
• Tuesday April 22, 2008, 12.00 to 13.00 PM
  
  Benoît GUILLAUME (Institute for Cancer Research)
  Identification of two new subtypes of 20S proteasomes and their role in tumor antigens processing
  
  
• Tuesday April 29, 2008, 12.00 to 13.00 PM
  
  Tong ZHANG
  Effect of APO866, an inhibitor of nicotinamide phosphoribosyletransferase, in human dendritic cells and post-transcriptional regulation of human IL-12 family

• Tuesday March 11, 2008, 12.00 to 13.00 PM

David Vermijlen
'Gammadelta T cell responses to human cytomegalovirus during fetal life'

• Tuesday February 5, 2008, 12.00 to 13.00 PM

Andrew BUSHELL (John Radcliffe Hospital, Nuffield Department of Surgery, Oxford,  United Kingdom)
In-vivo and ex-vivo generation of regulatory T cells that control allograft rejection. Do they work and which is best?

• Tuesday February 12, 2008, 12.00 to 13.00 PM

Common seminar IMI-IBMM
Etienne PAYS (ULB, Parasitologie moléculaire)
Mutual self-defence: the trypanolytic factor story
Auditorium Point Centre

• Tuesday February 19, 2008, 12.00 to 13.00 PM

Elke LEURIDAN and Pierre VAN DAMME (Centrum voor de Evaluatie van Vaccinaties, UIA, Antwerpen)
Persistence of maternal antibodies against vaccine preventable diseases in neonates 

• Tuesday February 26, 2008, 12.00 to 13.00 PM

Joanne RASSCHAERT (ULB, Laboratoire de Chimie biologique et de la Nutrition)
Molecular mechanisms involved in double-stranded RNA-induced pancreatic beta cell apoptosis

• Tuesday January 8, 2008, 12.00 to 13.00 PM

Michel GOLDMAN
Regulation of auto-immune responses: the complexity is growing 

• Tuesday January 15, 2008, 12.00 to 13.00 PM

Magali NOVAL RIVAS
Two types of immune regulatory mechanisms control chronic graft-versus-host disease

• Tuesday January 22, 2008, 12.00 to 13.00 PM

Stéphane TEMMERMAN
Attenuated expression of NEMO causes immune deficiency by impacting nucleosomal IKK-alpha activity 

• Tuesday January 29, 2008, 12.00 to 13.00 PM

Karen WILLARD-GALLO (Hématologie Expérimentale, Institut Bordet)
Targeting T-cell receptor gene expression in human diseases

• Tuesday December 4, 2007, 12.00 to 13.00 PM

Binita DUTTA 
CD4 T-cell responses to human cytomegalovirus infection during foetal life

• Tuesday December 11, 2007, 12.00 to 13.00 PM

Amandine LEGAT
(Structure et Fonction des Membranes Biologiques, ULB Unit 167)
A potential TLR-4 agonist: the cationic lipid diC14-amidine

• Tuesday November 6, 2007, 12.00 yo 13.00 PM
  
  Aurore DUBOIS
  Institute for Medical Immunology
  Regulation of allergy through activation of CD8⁺ T lymphocytes in early life?
  

• Tuesday November 13, 2007, 12.00 to 13.00 PM
  
  Bénédicte DANIS
  Institute for Medical Immunology
  Functional and molecular analyses of plasmacytoid dendritic cells in cord blood 

• Tuesday November 27, 2007, 12.00 to 13.00 PM
  
  Serge LEBECQUE
  Laboratoire de Génétique Moléculaire, Signalisation et Cancer, UMR5210, Université de Lyon, France
  TLR3: a therapeutic target in cancerology?
  

• Tuesday October 2, 2007, 12.00 to 13.00 PM
  
  Mustapha CHAMEKH
  Laboratoire de Bactériologie Moléculaire, Université Libre de Bruxelles 
  CD40-CD40L interaction in immunity against protozoan infections

• Tuesday October 9, 2007, 12.00 to 13.00 PM
  
  Nicole CUMBERBATCH
  IL-7 receptor function on T cells in HIV-infected individuals
  

• Tuesday October 16, 2007, 12.00 to 13.00 PM
  
  Jolyn JOHNSON
  The secret life of PKCs: implications in IFN-β and IL-12 regulation

• Tuesday October 23, 2007, 12.00 to 13.00 PM
  
  Bernhard RYFFEL
  UMR6218, Orléans, France
  Inflammasome activation and IL-1 in lung inflammation
  

• Tuesday October 30, 2007, 12.00 to 13.00 PM
  
  Alain LE MOINE
  Institute for Medical Immunology 
  Composite tissue allografts: how experimental models help immunologists for this new challenge
  

• Tuesday September 4, 2007, 12.00 to 13.00 PM
  
  Abdelhadi SAOUDI
  INSERM U563, Hôpital Purpan, Toulouse
  Identification of a new subset of natural regulatory CD8 T cells : functional analysis and genetic control

• Tuesday September 11, 2007, 12.00 to 13.00 PM
  
  Arnaud DIDIERLAURENT
  Kennedy Institute of Rheumatology, Imperial College, London
  Immune education of mucosal tissues : recovery from respiratory viral infection

• Tuesday September 25, 2007, 12.00 to 13.00 PM
  
  Nicolas MWAMBA TWITE
  Immune mechanisms involved in the control of human cytomegalovirus replication in epithelial cells