{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:46:05Z","timestamp":1787726765403,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The recent COVID\u201019 pandemic has highlighted a significant sex bias in disease outcome, where male sex is associated with greater disease severity and mortality. Interestingly, studies have also identified a role for antigen\u2010independent \u201cbystander\u2010activated\u201d CD8<jats:sup>+<\/jats:sup> T cells in the severity of COVID\u201019 and other viral infections. However, whether biological sex contributes to the magnitude of bystander T cell activation has not been investigated. To assess sex differences in bystander CD8<jats:sup>+<\/jats:sup> T cell activation, we isolated PBMCs from age\u2010matched male and female donors and stimulated the cells with cytokines IL\u201012\/15\/18 to induce bystander T cell activation. Male CD8<jats:sup>+<\/jats:sup> T cells stimulated with IL\u201015 exhibited greater bystander activation, including increased NKG2D expression and greater antigen\u2010independent cytotoxicity against tumor cells compared with female CD8<jats:sup>+<\/jats:sup> T cells. In contrast, IL\u201012\/18 and IL\u201012\/15\/18 stimulation of CD8<jats:sup>+<\/jats:sup> T cells did not reveal evidence of sex differences in bystander IFN\u2010\u03b3 production. Our data suggest that underlying sex differences in bystander CD8<jats:sup>+<\/jats:sup> T cell activation and cytotoxicity may contribute to the observed sex biases in disease severity of viral infections.<\/jats:p>","DOI":"10.1002\/eji.202451673","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T10:04:09Z","timestamp":1750759449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biological Sex Influences Human Bystander CD8<sup>+<\/sup> T Cell Activation"],"prefix":"10.1002","volume":"55","author":[{"given":"Elizabeth","family":"Balint","sequence":"first","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Medicine McMaster University  Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Joe","family":"Adaimy","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Medicine McMaster University  Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Montemarano","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Medicine McMaster University  Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana L.","family":"Portillo","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Medicine McMaster University  Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Ashkar","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Medicine McMaster University  Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0348-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2700-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-021-00410-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000709\u2010x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100870"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/PATHOGENS11010052"},{"key":"e_1_2_9_8_1","first-page":"1","article-title":"Epidemiologic and Clinical Parameters of West Nile Virus Infections in Humans: A Scoping Review","volume":"17","author":"Yeung M. 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