{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:31:42Z","timestamp":1768516302559,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,12]]},"group-title":"Immunology","reference-count":131,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Immunity to\n                  <jats:italic>Toxoplasma gondii<\/jats:italic>\n                  (\n                  <jats:italic>T. gondii<\/jats:italic>\n                  ) is sexually dimorphic in humans and mice, with females having higher morbidity and mortality during immune dysfunction and HIV-AIDS. The mechanisms underlying these sex differences are unclear. We investigated how a lack of CD4+ T cells (CD4 co-receptor KO) impacted\n                  <jats:italic>T. gondii<\/jats:italic>\n                  survival in mice. Female CD4 co-receptor KO mice succumbed to\n                  <jats:italic>T. gondii<\/jats:italic>\n                  much faster than males. To dissect why female CD4 co-receptor KO mice died faster, we tested their NK cell responses to acute\n                  <jats:italic>T. gondii<\/jats:italic>\n                  infection compared to males. Although in wild-type (WT) animals, both sexes had similar increases in total NK cells and IFN\u03b3 + NK cells, infected CD4 co-receptor KO female mice had 50% fewer IFN\u03b3+ NK cells than infected WT female mice. Infected male CD4 co-receptor KO had a similar increase in IFN\u03b3+ NK cells as WT male mice. Since CD4 co-receptor deficient mice still have functional helper T cells that are CD4\u2212, we next tested survival and NK cell responses in female and male MHCII deficient (MHCIIKO) animals, which completely lack helper CD4+T cells. Surprisingly, survival, NK cell numbers, and IFN\u03b3+ NK cells were not significantly different between WT or MHCIIKO female and male mice. These results suggest CD4 co-receptor expression is required for survival via optimal NK cell responses during acute\n                  <jats:italic>T. gondii<\/jats:italic>\n                  infection only in female mice and not in male mice. Our findings reveal an unappreciated sexual dimorphic role of CD4 co-receptor expression in regulating NK cell responses to acute\n                  <jats:italic>T. gondii<\/jats:italic>\n                  infection.\n                <\/jats:p>","DOI":"10.1101\/2024.12.06.627254","type":"posted-content","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T23:21:47Z","timestamp":1734045707000},"source":"Crossref","is-referenced-by-count":0,"title":["CD4 Co-Receptor Regulates Sex-Specific NK Cell Responses to Acute\n                  <i>Toxoplasma gondii<\/i>\n                  Infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6692-1852","authenticated-orcid":false,"given":"Tathagato","family":"Roy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hunter K.","family":"Keplinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaatje","family":"Fisk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai K.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen L.","family":"Denton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8805-4561","authenticated-orcid":false,"given":"Jason P.","family":"Gigley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024121403401346000_2024.12.06.627254v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16412-X"},{"key":"2024121403401346000_2024.12.06.627254v1.2","doi-asserted-by":"publisher","DOI":"10.1258\/ijsa.2012.012189"},{"key":"2024121403401346000_2024.12.06.627254v1.3","doi-asserted-by":"publisher","DOI":"10.4103\/0974-777X.145248"},{"key":"2024121403401346000_2024.12.06.627254v1.4","first-page":"S61","article-title":"Cerebral toxoplasmosis after renal transplantation. 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