Alloantigen-enhanced accumulation of CCR5⁺ 'effector' regulatory T cells in the gravid uterus

Regulatory T cells play an essential role in preventing fetal rejection by the maternal immune system. Here we show that, based on the expression of CCR5, regulatory T cells can be divided into a highly suppressive CCR5⁺ and a far less suppressive CCR5⁻ subpopulation, suggesting that the former represent the effector arm of regulatory T cells. Although regulatory T cells from CCR5⁻/⁻ gene deletion mutants still suppress, they are less effective mediators of maternal-fetal tolerance. The accumulation of CCR5⁺ regulatory T cells at this site appears to be enhanced by alloantigen. This finding is in stark contrast to the systemic expansion of regulatory T cells during pregnancy, which appears to be alloantigen-independent. The fact that CCR5⁺ regulatory T cells preferentially accumulate in the gravid uterus and that expression of CCR5 on regulatory T cells can be induced by activation lead us to propose that CCR5 is responsible for the accumulation of those regulatory T cells that have been activated by paternal antigens.