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Occult losses can represent T cell-mediated rejection, and antigen-specific regulatory T cells (Tregs) with classical \u03b1\u03b2 T cell receptors (TcR) activated by semen antigens at the time of mating are protective. If there is no occult loss, an inadequate Treg response can also predispose to RM. In RM, proinflammatory cytokines from natural killer (NK)-type cells and macrophages of the innate immune system are responsible and cells with \u03b3\u03b4 TcR protect via release of TGF-\u03b2-type molecules. Immunization of abortion-prone female CBA\/J mice or administration of cell-associated or soluble CD200, an immune check point inhibitor, can prevent abortions by augmenting uterine decidual suppressor cell activity. Human studies suggest that is also true in couples with RM. Environmental activators of the innate immune system, such as bacterial LPS and stress, can cause abortions as well as occult losses. The endogenous level of Tregs and activation of Tregs specific for the male H-Y antigen may determine success rates and alter the male:female birth ratio. Intralipid alters LPS clearance, prevents abortions in the CBAxDBA\/2 model, and is effective in increasing live birth rates in couples undergoing IVF treatment.<\/jats:p>","DOI":"10.1042\/etls20200042","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T09:26:08Z","timestamp":1595323568000},"page":"207-227","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["On use of animal models"],"prefix":"10.1042","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8032-1028","authenticated-orcid":false,"given":"David A.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Medicine, Pathology and Molecular Medicine, Health Science Centre Rm. 3H2, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada L8S 4K1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"2021111608143025300_ETLS-2020-0042CC1","volume-title":"The Logic of Scientific Discovery","year":"2002"},{"key":"2021111608143025300_ETLS-2020-0042CC2","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: differences between mouse and human immunology","volume":"172","year":"2004","journal-title":"J. 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