Homeostasis and anergy of CD4+CD25+ suppressor T cells in vivo

CD4(+)CD25(+) suppressor T (T-5) cells play a critical role in the maintenance of peripheral tolerance. We examined here proliferative and functional responses as well as differential gene expression in T-s cells. We found that Ts cells were hyporesponsive to antigenic stimuli in vivo and unable to flux Ca2+ upon T cell receptor (TCR) engagement. However, T-s cells were not impaired in their proliferative response to lymphopenia, which was dependent on major histocompatibility complex class 11 expression. Homeostatic proliferation did not abolish T-s cell anergy; rather, it substantially augmented T-s cell function. DNA array analyses identified genes that may inhibit responsiveness at a number of levels in multiple signaling cascades in T-s cells, as well as several anti-apoptotic genes that may mediate their survival.