Homeostatic expansion and phenotypic conversion of naive T cells in response to self peptide/MHC ligands

Recent data suggest that survival of resting, naive T cells requires an int eraction with self MHC molecules. From analysis of the class I MHC-restrict ed T cell receptor transgenic strain OT-1. we report a different response. Rather than merely surviving, these T cells proliferated slowly after trans fer into T-depleted syngeneic hosts. This expansion required both T cell "s pace" and expression of normal levels of self class I MHC molecules. Furthe rmore, we demonstrate that during homeostatic expansion in a suitable envir onment, naive phenotype (CD44(low)) OT-1 T cells converted to memory phenot ype (CD44(med/high)), despite the absence of foreign antigenic stimulation. On the other hand, cells undergoing homeostatic expansion did not acquire cytolytic effector function. The significance of these data for reactivity of T cells with self peptide/MHC ligands and the implications for normal an d abnormal T cell homeostasis are discussed.