It is well established that the immaturity of the innate system at birth is associated with a distinct pattern of CD4 helper T cell responses, resulting in impaired Th1-type responses against intracellular pathogens and enhanced Th2-type allergic responses. We identified in the mouse several factors responsible for this skewing, including deficient upregulation of CD40 ligand (CD154) on and increased production of interleukin-4 by neonatal CD4 T cells. We will now further explore how dendritic cells and CD8 T cells shape CD4 T cell responses in early life. Regarding dendritic cells, we will focus our attention on the balance between interleukin-12 family members produced in response to Toll-like receptor ligands in vivo as this balance critically influences the outcome of helper T cell responses upon infection or vaccination. The phenotype of CD8 T cells controlling Th2 responses in early life and the role of interferon-gamma in their regulatory action will be specifically considered. Furthermore, we will develop new tools to study the development of Th17 and follicular helper T cells in the neonatal period as these recently identified T cell subsets appear to play key roles in the host defenses against extra-cellular pathogens.

Principal investigator: Véronique FLAMAND (PhD)
Associate investigator: Fabienne WILLEMS (PhD)
Post-doctoral fellows: Kathy JAWORSKY, David TORRES
MD-PhD student: Brigitte ADAMS
PhD students: Aurore DUBOIS, Isabelle DEBOCK
Technical assistant: Sandrine DELBAUVE

de Lavareille A, Prigogine C, Paulart F, Nagy N, Habran C, Haddou NO, Le Moine A, Salmon I, Goldman M, Flamand V. Regulatory role of host CD8+ T lymphocytes in experimental graft-versus-host disease across a single major histocompatibility complex class II incompatibility. Transplantation 2005; 80(9):1293-9

Adams B, Nagy N, Paulart F, Vanderhaeghen ML, Goldman M, Flamand V. CD8+ T lymphocytes regulating Th2 pathology escape neonatal tolerization.  J Immunol 2003;171(10):5071-6

Flamand V, Donckier V, Demoor FX, Le Moine A, Matthys P, Vanderhaeghen ML, Tagawa Y, Iwakura Y, Billiau A, Abramowicz D, Goldman M. CD40 ligation prevents neonatal induction of transplantation tolerance. J Immunol 1998;160(10):4666-9.

Donckier V, Flamand V, Desalle F, Vanderhaeghen ML, de Veerman M, Thielemans K, Abramowicz D, Goldman M. IL-12 prevents neonatal induction of transplantation tolerance in mice.  Eur J Immunol. 1998;28(4):1426-30

Government of the Walloon Region
GSK Biologicals
The Fund for Scientific Research (F.R.S - FNRS) and the Télévie Programme
The Belgian Science Policy
The European Commission
The Erasme Fund The Wiener-Anspach Foundation
The Belgian Kid's Fund
The Roche Organ Transplantation Research Foundation
The Dimitris and Noela Nakos Foundation
Roche Pharmaceuticals, Belgium
Wittycell S.A.S