{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:48:15Z","timestamp":1790876895151,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Seminal fluid provides for the carriage and nutrition of sperm, but also modulates immunity to prevent allo-rejection of sperm by the female. Immune suppression by seminal fluid has been associated with extracellular vesicles, originally termed prostasomes, which contain CD52, a glycosylated glycophosphoinositol-anchored peptide released from testicular epithelial cells. Previously, we reported that human T cell-derived CD52, bound to the danger-associated molecular pattern protein, high mobility group box 1 (HMGB1), suppresses T cell function via the inhibitory sialic acid-binding immunoglobulin-like lectin-10 (Siglec-10) receptor. Here we show that human seminal fluid contains high concentrations of CD52 complexed with HMGB1, which mediates T cell suppression indirectly via Siglec-7 on antigen-presenting cells. Proliferation of natural killer (NK) cells, which express Siglec-7 and play a key role in the immune defence of the uterus, was directly suppressed by seminal fluid CD52. These findings elucidate a critical function of seminal fluid to suppress cellular immunity and facilitate reproduction.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1497889","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T05:10:48Z","timestamp":1734325848000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Soluble CD52 mediates immune suppression by human seminal fluid"],"prefix":"10.3389","volume":"15","author":[{"given":"Leonard C.","family":"Harrison","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie L.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Bandala-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D.","family":"Huntington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert I.","family":"McLachlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai","family":"Rautela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira K.","family":"O\u2019Bryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"B1","article-title":"Inhibition of PHA-induced lymphocyte transformation by human semen","volume":"45","author":"Davis","year":"1974","journal-title":"17th Int Cong South Afr Soc Obstet Gynecol (Pretoria)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/253727a0","article-title":"Suppressive effect of seminal fluid on lymphocyte activation","volume":"253","author":"Stites","year":"1975","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a136156","article-title":"Immunosuppressive mechanisms in semen: implications for contraception","volume":"10","author":"Kelly","year":"1995","journal-title":"Hum Reprod"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18881-2_6","article-title":"Seminal fluid signalling in the female reproductive tract: implications for reproductive outcome and offspring health","volume":"868","author":"Schjenken","year":"2015","journal-title":"Adv Exp Med Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.136.8.2862","article-title":"Suppression of natural killer cell activity by human seminal plasma in vitro: identification of 19-0H-PGE as the suppressor factor","volume":"136","author":"Tarter","year":"1986","journal-title":"J Immunol"},{"key":"B6","article-title":"Seminal plasma suppression of human lymphocyte responses in vitro requires the presence of bovine serum factors","volume":"66","author":"Vallely","year":"1986","journal-title":"Clin Exp Immunol"},{"key":"B7","article-title":"Immunosuppression by seminal prostaglandins","volume":"75","author":"Quayle","year":"1989","journal-title":"Clin Exp Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1600-0897.1993.tb00594.x","article-title":"Transforming growth factor \u03b2 as an immunosuppressive protein in human seminal plasma","volume":"30","author":"Nocera","year":"1993","journal-title":"Mol Hum Reprod"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(02)00015-3","article-title":"Transforming growth factor \u03b2-a mediator of immune deviation in seminal plasma","volume":"57","author":"Robertson","year":"2002","journal-title":"J Reprod Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1991.tb02968.x","article-title":"Extracellular organelles (prostasomes) are immunosuppressive components of human semen","volume":"86","author":"Kelly","year":"1991","journal-title":"Clin Exp Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118594","article-title":"GPI-anchored complement regulatory proteins in seminal plasma. 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