Abstract
How regulatory T cells (Treg) control autoreactive T cells has not been analyzed in animals with a normal T cell repertoire. Using endogenous viral superantigens (VSAg) as the primary self antigens and mice with the Scurfy mutation of FoxP3, we show here that the Treg defect causes preferential accumulation of autoreactive T cells. Interestingly, in the Scurfy mice, the proliferation of VSAg-reactive T cells was no more vigorous than that of non-VSAg-reactive T cells, which indicated that the preferential accumulation is not due to preferential proliferation. In contrast, VSAg-reactive T cells disappears in WT host despite their preferential proliferation. Importantly, when adoptively transferred into the newborn Scurfy mice, the Treg selectively kill autoreactive T cells without affecting their proliferation. The selective elimination is due to increased susceptibility of autoreactive T cells to Treg-mediated killing.