Characterization of dysfunctional human CD8+T cells specific for viral antigens or self proteins

• Applicant: Dr. Cécile Gouttefangeas
• Subject Area: Immunology
• Term: from 2004 to 2005
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5433950

We have previously identified peripheral populations of CD8+T cells, carrying T-cell receptors specific for tumor- or viral-associated antigen-derived peptides, which show a decreased responsiveness to antigen-specific in vitro stimulation. Moreover, we could show that, at least for some of these populations, their phenotype resembles that described for terminally-differentiated effector cells or senescent cells. The exact function of such T cells is so far unknown. The aim of this project is to characterize these dysfunctional T cells, both at the phenotypic and functional levels, model them using long-term culture techniques and attempt to manipulate their function in vitro. In addition, screening for these dysfunctional T-cells ex vivo in tumor-bearing patient and the elderly should contribute to an understanding of their physiological role. Thus, we aim to test the working hypothesis that chronic antigenic stress in cancer and ageing results in T-cell dysfunction which compromises effective immunity. The project will marry expertise and resources from two complementary groups to test this hypothesis by examining CD8+ T cells from different sources.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Graham Pawelec