CD4(+)CD25high 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(+)CD25high T cells are the only cells which exhibit regulatory function in humans. Humans CD4(+)CD25low cells have no ability for immunosuppression. CD4(+)CD25high 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-beta. 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.
Saito
Shigeru
S
Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan. s30saito@ms.toyama-mpu.ac.jp
Sasaki
Yasushi
Y
Sakai
Masatoshi
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10 / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014366:Tryptophan Oxygenase / Q000096:biosynthesis
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D014366:Tryptophan Oxygenase