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Activation of CD8⁺ Regulatory T Cells by Human Placental Trophoblasts¹

Ling Shao^2,*, Adam R. Jacobs, Valrie V. Johnson and Lloyd Mayer^*

^* Immunobiology Center and Department of Obstetrics and Gynecology, Mount Sinai School of Medicine, New York, NY 10029

The immunological basis by which a mother tolerates her semi-allogeneic fetus remains poorly understood. Several mechanisms are likely to contribute to this phenomenon including active immune regulation by regulatory T cells. In this article, we report that human placental trophoblasts activate a clonal population of CD8⁺ T cells with regulatory function. These cells are not MHC class I restricted, but require costimulation through a member of the carcinoembryonic Ag family present on early gestation trophoblasts. These regulatory T cells express the mucosal markers CD101 and CD103 and display selective usage of the TCR gene V9. CD8⁺ T cells isolated from the peripheral blood of pregnant mothers (16–28 wk) also demonstrate expansions in the same V family (V9), signaling a possible role for these cells in preventing fetal rejection in vivo. We have previously characterized a subset of CD8⁺ regulatory T cells activated by the combination of the nonclassical class I molecule CD1d and a costimulatory molecule of the carcinoembryonic Ag family present on the intestinal epithelium. These data support the concept that distinct regulatory T cell populations exist at different sites and may be regulated locally by unique restriction elements, costimulatory signals, and Ags.

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