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Suppression of CD8+T cells is necessary for a tolerogenic environment that promotes implantation and pregnancy. However, the mechanisms regulating this process remain unclear. Sex hormones are known to control immune responses directly on immune cells and indirectly through the tissue environment. When the actions of estradiol (E<jats:sub>2<\/jats:sub>), progesterone (P) and TGF\u03b2 on EM CD8+T cells were evaluated, cytotoxic activity, perforin and granzymes were directly suppressed by E<jats:sub>2<\/jats:sub>and TGF\u03b2 but not P. Moreover, incubation of polarized EM epithelial cells with P, but not E<jats:sub>2<\/jats:sub>, increased TGF\u03b2 secretion. These findings suggest that E<jats:sub>2<\/jats:sub>acts directly on CD8+T cell to suppress cytotoxic activity while P acts indirectly through induction of TGF\u03b2 production. Understanding the mechanisms involved in regulating endometrial CD8+T cells is essential for optimizing reproductive success and developing protective strategies against genital infections and gynecological cancers.<\/jats:p>","DOI":"10.1038\/s41598-021-81380-8","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T11:09:05Z","timestamp":1611054545000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Direct and Indirect endocrine-mediated suppression of human endometrial CD8+T cell cytotoxicity"],"prefix":"10.1038","volume":"11","author":[{"given":"Z.","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rodriguez-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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