CD4⁺CD25^high regulatory T cells in human pregnancy

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.