Jean Davoust is CNRS Research Director and Immunologist, gained a Ph.D. in membrane biophysics, was trained in cell biology and physical instrumentation at EMBL (Heidelberg, Germany), pioneered confocal imaging in France (CIML, Marseilles), deciphered MHC class II trafficking and antigen presentation in dendritic cells and joined the Baylor Institute for Immunology Research (BIIR, Dallas TX) to settled new immunization strategies for anti-tumor immunotherapy. With David Gross we developed a novel strategy to induce antigen-specific tolerance with regulatory T cells tailored for gene therapy applications achieved with recombinant AAV vectors. J. Davoust has a dual expertise in immunology and confocal imaging, and devoted his career to unraveling MHC presentation processes and T cell mediated regulation of adaptive immune responses.
J. Davoust authored 98 publications with over 13000 citations, H index 49.
Our laboratory studies the recruitment of regulatory T lymphocytes with applications in gene and cell therapies. We wish manipulate antigen presentation pathways to induce immune tolerance to novel medicine gene therapy interventions.
Regulatory T (Treg) cells are particularly important to maintain self-tolerance, shield spontaneous activation of autoreactive T cells in inflamed tissues and are mandatory to maintain immune homeostasis at environmental interfaces. Treg cells are also instrumental to promote immune tolerance to grafts and to medicinal products or therapeutic transgenes delivered with viral vectors.
Our laboratory addresses the mechanisms governing homeostasis and function of CD4+ Foxp3+ regulatory T lymphocytes with defined applications in the field of gene and cell therapies. Regarding the mode of action and the suppression-efficiency of antigen-specific Treg cells expressing a defined T cell receptor, we established that:
Major areas of interest of our team include:
Treg cells are educated in the thymus by unresolved antigen-specific interactions as a diversion of the CD4+ T cell lineage, whereas a minor proportion of Treg cells emerge in the periphery by conversion of conventional CD4+ T cells. The relationship between antigen-specific Treg cells education in the thymus and their functional activation in the periphery is unresolved. Moreover, the recruitment of antigen-specific Treg cells leading to induction of dominant tolerance to foreign antigens is difficult to reach and antigenic determinants recognized by Treg cells have not been characterized at the molecular level.
To approach these questions we explore:
Our long-term perspective is to manipulate antigen presentation pathways and mobilize antigen-specific Treg cells in order to induce tolerance to foreign antigens in regenerative medicine applications. Moreover, we expect that these modalities will be important to restore tissue-specific tolerance in autoimmunity patients.