Goldman M. Sublingual immunotherapy: the quest for innovative adjuvants. Clin Exp Allergy 2008 ; 38:1705-1706.

Sublingual immunotherapy (SLIT) has been established in humans as a safe and efficacious treatment for type I respiratory allergies. OBJECTIVE: In this study, we compared three Toll-like receptor (TLR) 2 ligands (Pam3CSK4, Porphyromonas gingivalis lipopolysaccharide and lipoteichoic acid) as potential adjuvants for sublingual allergy vaccines. METHODS: These molecules were tested in co-cultures of adjuvant-pre-treated dendritic cells (DCs) with murine naïve CD4(+) T lymphocytes. Patterns of cytokine production, phenotype, proliferation and gene expression were analysed by ELISA, cytofluorometry and quantitative PCR, respectively. TLR2 ligands were subsequently tested in a model of SLIT in BALB/c mice sensitized with ovalbumin (OVA). RESULTS: Among the three TLR2 ligands tested, the synthetic lipopeptide Pam3CSK4 is the most potent inducer of IL-12p35 and IL-10 gene expression in murine bone marrow-derived DCs, as well as in purified oral myeloid DCs. Only Pam3CSK4-treated DCs induce IFN-gamma and IL-10 secretion by naïve CD4(+) T cells. Sublingual administration of Pam3CSK4 together with the antigen in BALB/c mice sensitized to OVA decreases airway hyperresponsiveness as well as OVA-specific T-helper type 2 (Th2) responses in cervical lymph nodes dramatically.

Li Z, Benghiat FS, Charbonnier LM, Kubjak C, Noval Rivas M, Cobbold SP, Waldmann H, De Wilde V, Petein M, Schuind F, Goldman M, Le Moine A.  CD8+ T-cell depletion and rapamycin synergize with combined coreceptor / stimulation blockade to induce robust limb allograft tolerance in mice. Am J Transplant 2008 ; 8:1-10.

The growing development of composite tissue allografts (CTA) highlights the need for tolerance induction protocols. In the present study, Alain Le Moine and his research team developed a mouse model of heterotopic limb allograft in a stringent strain combination in which potentially tolerogenic strategies were tested taking advantage of donor stem cells in the grafted limb. The results of their research show that robust CTA tolerance and mixed donor-recipient chimerism can be achieved in response to the synergizing combination of rapamycin, transient CD8(+) T-cell depletion and costimulation/coreceptor blockade.

Finan C, Ota MOC, Marchant A, Newport MJ. Natural variation in immune responses to neonatal Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccination in a cohort of gambian infants. PLoS ONE 2008 ; 3 : e3485.

Although BCG is widely given to neonates, IFN-γ responses to BCG in this age group are poorly described. Characterisation of IFN-γ responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. The results of this study show that cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine variation in IFN-γ responses.

De Wilde V, Benghiat FS, Noval Rivas M, Lebrun JF, Kubjak C, Oldenhove G, Verdebout JM, Goldman M, Le Moine A. Endotoxin hyperresponsiveness upon CD4(+) T cell reconstitution in lymphopenic mice: control by natural regulatory T cells. Eur J Immunol 2008 ; 38:48-53.

This paper demonstrate that the transfer of T lymphocytes into mice devoid of T and B cells dramatically enhances the inflammatory response to lipopolysaccharide, a major bacterial toxin. This observation shed light on the risk of septic shoc upon hematopoietic stem cell or bone marrow transplantation in immunodeficient children or patients with cancer.

Stubbe M, Vanderheyde N, Pircher H, Goldman M, Marchant A. Characterization of a subset of antigen-specific human central memory CD4⁺ T lymphocytes producing effector cytokines. Eur J Immunol 2008 ; 38:273-282.

This paper reviews the characterization of novel features of memory T lymphocytes in humans. This work might lead to the development of new tools to monitor immune responses to vaccines.

Danis B, George TC, Goriely S, Dutta B, Renneson J, Gatto L, Fitzgerald-Bocarsly P, Goldman M, Willems F, De Wit D. Interferon regulatory factor 7-dependent responses are deficient in cord blood plasmacytoid dendritic cells. Eur J Immunol 2008 ; 37:507-517.

This paper provides a molecular basis for the decreased ability of plasmacytoid dendritic cells in cord blood to produce type I interferons.  The observation of a defect in the expression of genes depending of the transcription factor IRF7 might explain the increased susceptibility of human newborns to severe viral infections.  Furthermore, it is relevant to the use of umbilical cord blood for hematopoietic stem cell transplantation in patients with leukemia or congenital immunodeficiency.

Goriely S, Goldman M. Interleukin-12 family members and the balance between rejection and tolerance. Curr Opin Organ Transplant 2008 ; 13:4-10.

This paper highlights recent findings on the function of different IL-12 family members: IL-12p70, IL-27 and IL-35 and discuss their possible involvement in influencing the balance between graft rejection and tolerance. Allograft rejection involves multiple effector mechanisms. Interleukin (IL)-12 family members play a critical role in influencing helper T-cell differentiation and inflammatory processes, and their critical role in orchestrating inflammation of autoimmune or infectious origin starts to be unravelled.

Goriely S, Neurath M, Goldman M. How microorganisms tip the balance between interleukin-12 family members. Nature Rev Immunol 2008; 8:82-86.

This paper reviews recent evidence suggesting that Toll-like receptor ligands, in association with other microbial products and endogenous mediators, can control the balance between the expression of interleukin-12 cytokine family members, thereby directly regulating the outcome of T-cell-mediated inflammatory responses. On this basis, the authors present a novel perspective on the pathogenesis and regulation of inflammatory disorders.