CD4 +CD25 high regulatory T cells in human pregnancy

Abstract

In both rodent and human systems, there is an emerging consensus that immunoregulatory activity specific for donor alloantigens is enriched in the CD4 +CD25 + T cell population. The absence of CD4 +CD25 + regulatory T (Treg) cells induces severe immunodeficiency with autoimmune disease, dermatitis and fatal infections in humans and mice. CD4 +CD25 + Treg cells play a critical role in peripheral tolerance, transplantation tolerance and maternal tolerance to the fetus. Although both human and mouse CD4 +CD25 + Treg have potent regulatory properties, surface phenotypes of human CD4 +CD25 + Treg cells are not exactly the same as those of mouse CD4 +CD25 + Treg cells. Murine CD4 +CD25 + T cells are homogenous and exhibit regulatory function. On the other hand, CD4 +CD25 high T cells are the only cells which exhibit regulatory function in humans. Humans CD4 +CD25 low cells have no ability for immunosuppression. CD4 +CD25 high T cells inhibit the immunostimulation of conventional T cells through cell-to-cell contact or immunosuppressive cytokines such as interleukin 10 and transforming growth factor-β. As another mechanism of immunosuppression, CTLA-4 on CD4 +CD25 + regulatory T cells up-regulate indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells which play important roles for immunosuppression. Here, we review the differences between humans and mouse Treg cells and the role of CD4 +CD25 +Treg during pregnancy.