Activation of CD8+ regulatory T cells by human placental trophoblasts.
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 Vbeta9. CD8(+) T cells isolated from the peripheral blood of pregnant mothers (16-28 wk) also demonstrate expansions in the same Vbeta family (Vbeta9), 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.
Shao
Ling
L
Immunobiology Center and Department of Obstetrics and Gynecology, Mount Sinai School of Medicine, New York, NY 10029, USA. ling.shao@mssm.edu
Jacobs
Adam R
AR
Johnson
Valrie V
VV
Mayer
Lloyd
L
D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000096:biosynthesis; D055610:Antigens, CD1d; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010920:Placenta / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000951:Antigens, Neoplasm; C093213:CD101 antigen, human; C526877:CD1D protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; D039001:Integrin alpha Chains; D008562:Membrane Glycoproteins; C091367:alpha E integrins