Head of the clinical immunology laboratory of the Insitut Curie
Co-Director of the IGR-IC INSERM biotherapy investigational unit
Group leader Inserm U932,
Chairman of the Institut Curie Immunotherapy Network,
2001-: Group leader Inserm U932, CD4 Lymphocyte and anti-tumoral response
2000-: Head of the clinical immunology laboratory of the Curie Institute
1990-2000: Associate Professor in Immunology Univ. Paris XI. Kremlin-Bicetre hospital
1997-2000: Group leader Inserm U25, Necker Hospital
1995-1996: Group leader, Inserm U267, Villejuif,
1992-1994 : Visiting fellow in the LCMI, NAID, NIH in Polly Matzinger group.
1986-1992 : Ph.D training, CNRS, Villejuif
1986-1990: Fellow in Nephrology (tranplantation unit).
1997: Habilitation to direct research (HDR)
1990: PhD Thesis, Paris XI, Centre d'Orsay
1986: Medical thesis (Paris XI)
1982-84 : "Diplôme d'étude et de recherche en biologie humaine", St Louis Hospital.
1980-82 and 1984-86 : "Interne des hopitaux de Paris", Residency
Our group studies in vivo T cell biology in mouse and human models.
We are focusing on three main topics:
1) Study of the mucosal associated invariant T (MAIT) cells: an evolutionarily conserved T cell selected by MHC-related protein I (MR1) on gut B cells.
We have discovered a T cell sub population whose specificity is conserved between species characterized by the use of an invariant chain, the Vα7.2/19-Jα33 TCRα chain. These cells are localized in the gut lamina propria and require the presence of B cells in the same location both in humans and in mice. These T cells are now called Mucosal associate invariant T cells (MAIT) and are selected by the MHC related molecule 1, MR1 which is also highly conserved between species.
We showed that MAIT cells development is a stepwise process with an intra-thymic MR1 dependent but B cell and commensal flora independent selection process followed by a peripheral maturation and expansion requiring B cells and the commensal flora.
We recently found that MAIT cells are activated and secrete Interferon-g after stimulation by fibroblasts or antigne presenting cells co-cultured with bacteria and yeasts but not viruses. MAIT can also secrete IL-17. MAIT cells migrate to the site of bacterial infection both in humans and mice. They display protective function in 2 models of infectious disease.
The ligand bound to MR1 and recognized by MAIT cells is currently under study.
2) CD4+ T cell physiology
Although T cells proliferate extensively during an immune response, they do not expand indefinitely. We have found a negative feedback loop regulating CD4 T cell proliferation in which antigen experienced T cells are selectively excluded from an ongoing immune response (Fig. 1). The mechanisms involved in this phenomenon are currently being investigated.
3) Study of the interactions between tumors expressing nominal antigens in a constitutive or inducible way and specific T cells
Our goal is to better understand the relationship between tumors expressing a nominal antigen at a given time and location, and a minimal immune system specific for that same antigen. Using transplantable tumor models expressing antigen in an inducible manner or spontaneous tumor models expressing nominal antigens, we try to decipher whether the tumor is ignored or leads to deletion, anergy or class switch of the specific immune response or generate suppressor T cells.
These same models are used to develop new anti-cancer vaccines based on long peptide or DNA vaccination targeting the antigen to antigen presenting cells.