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

CD4+CD25+ suppressor T (TS) 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 TS 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, TS cells were not impaired in their proliferative response to lymphopenia, which was dependent on major histocompatibility complex class II expression. Homeostatic proliferation did not abolish TS cell anergy; rather, it substantially augmented TS cell function. DNA array analyses identified genes that may inhibit responsiveness at a number of levels in multiple signaling cascades in TS cells, as well as several anti-apoptotic genes that may mediate their survival.