Abstract : The composition of T lymphocyte's compartments is constantly modified, because of the production of new TCR specificities, selection after antigen encounter and cell death. In order to control the cell transition between central and peripheral compartments, mechanisms of homeostatic regulation maintain the immune system in a steady-state. As seen in any ecosystem, T lymphocytes are in competition for limited selection niches and resources. During this thesis, we have used mice in order to analyse the behaviour of CD8+ T ab lymphocytes after an environmental perturbation. We have also used MHC class I molecules as a model of resource necessary for CD8+ T cell survival.
We have first studied central and peripheral selection of CD8+ T cells double-transgenic for the male-specific TCR aHY and the TCR P14, specific for the the epitope gp33-41 from the lymphocytic choriomeningitis virus (LCMV). This mouse model is representative of a common phenomenon in the immune system, since 30% of human and mouse T cells can express two different TCRs at their surface. Our results show that the expression of two TCRs is sufficient to escape partially to negative selection in the thymus, and to resist to clonal deletion at the periphery. We have next analysed the establishment of LCMV chronic infection in mice expressing only the P14 TCR (MoP14 mice). We could observe the selective emergence of viral mutants, all specifically mutated in the epitope gp33-41, and a modification of the functional behaviour of CD8+ T cells in the chronically infected animals. Altogether, these data suggest that CD8+ T cells adapt to their environmental conditions.
Finally, we have focused our attention on the survival and homeostatic proliferation of CD8+ T cells, by studying the influence of MHC class I molecules in these processes. Our results indicates that the T cell fate is directly linked with the cross-reactivity of the different TCRs used in our experiments.