Survival and homeostatic proliferation of naive peripheral CD4(+) T cells in the absence of self peptide : MHC complexes

TCR-self peptide:MHC interactions play a critical role in thymic positive s election, yet relatively little is known of their function in the periphery . It has been suggested that continued contact with selecting MHC molecules is necessary for long-term peripheral maintenance of naive T cells. More r ecent studies have also demonstrated a role for specific self peptide:MHC c omplexes in the homeostatic expansion of naive T cells in lymphopenic mice. Our examination of these processes revealed that, whereas self class II MH C molecules do have a modest effect on long-term survival of individual CD4 (+) T cells, interactions with specific TCR ligands are not required for pe ripheral naive CD4(+) T cell maintenance. In contrast, selective engagement of TCRs by self-peptide:MHC complexes does promote proliferation of CD4(+) T cells under severe lymphopenic conditions, and this division Is associat ed with an activation marker phenotype that is different from that induced by antigenic stimulation. Importantly, however, the ability of naive T tell s to divide in response to homeostatic stimuli does not appear to be string ently dependent on TCR-self peptide:MHC interactions. Therefore, these resu lts show that the factors regulating survival and homeostatic expansion of naive T cells in the periphery are not identical. In addition, we provide e vidence for a novel form of T cell proliferation that can occur independent ly of TCR signaling and suggest that this reflects another mechanism regula ting homeostatic T cell expansion.