Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivo

The failure of CD25(+) regulatory T cells (T-regs) to proliferate after T cell receptor (TCR) stimulation in vitro has lead to their classification as naturally anergic. Here we use T-reg, expressing a transgenic TCR to show that despite anergy in vitro, T-regs proliferate in response to immunization in vivo. T-regs also proliferate and accumulate locally in response to transgenically expressed tissue antigen whereas their CD25(-) counterparts are depleted at such sites. Collectively, these data suggest that the anergic state that characterizes CD25(+) T-regs in vitro may not accurately reflect their responsiveness in vivo. These observations support a model in which T-reg population dynamics are shaped by the local antigenic environment.