Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state

Despite a growing interest in CD4(+) CD25(+) regulatory T cells (T-reg) that play a major role in self-tolerance and immunoregulation, fundamental parameters of the biology and homeostasis of these cells are poorly known. Here, we show that this population is composed of two T-reg subsets that have distinct phenotypes and homeostasis in normal unmanipulated mice. In the steady state, some T-reg remain quiescent and have a long lifespan, in order of months, whereas the other Treg are dividing extensively and express multiple activation markers. After adoptive transfer, tissue-specific T-reg rapidly divide and expand preferentially in lymph nodes draining their target self-antigens. These results reveal the existence of a cycling Treg subset composed of autoreactive Treg that are continuously activated by tissue self-antigens.