Role of major histocompatibility complex class II molecules in the maintenance of CD4 memory T cell function

The inheritable modifications that occur during activation enable memory T cells to mount a faster and stronger immune response than naive cells upon re-encounter with the same antigen. Memory CD4 T cells do not require MHC class II contact for survival, but previous analyses from our lab have underlined important differences between CD4 T cells transferred in MHC class II competent or deficient hosts that question the complete independency of memory cells from signals derived from MHC class II contact in terms of functionality. In this study, resting memory CD4 T cells generated in MHC class II competent or deficient hosts were characterised at the molecular level by analysis of gene expression with the aim to identify potential mechanisms to explain how MHC class II molecules preserve memory CD4 T cell function. Candidate molecules highlighted by analysis of gene expression were further investigated using FACS analysis and in vitro and in vivo experiments. As the phenotypic and functional characteristics of memory CD4 T cells generated in MHC class II deficient hosts were found established already in the early stages of the memory phase, the analysis was extended to the effector phase. The results obtained indicated that CD4 T cells may not achieve an optimal differentiation into effector cells in MHC class II deficient hosts suggesting that CD4 T cells require non-cognate interactions with MHC class II molecules during activation. Therefore, a universal role of MHC contact with non-antigen presenting MHC molecules during the initial activation step may be instrumental in shaping the functional competence of memory T cells