{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:10:46Z","timestamp":1785413446721,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,27]]},"group-title":"Immunology","reference-count":106,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01 AI141435"],"award-info":[{"award-number":["R01 AI141435"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AI172111"],"award-info":[{"award-number":["R01 AI172111"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AI123323"],"award-info":[{"award-number":["AI123323"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AI007140"],"award-info":[{"award-number":["AI007140"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>ABSTRACT\/SUMMARY<\/jats:title>\n                <jats:p>Many pathogenic human infections enter the host via a mucosal surface. These nonlymphoid tissues are abundantly populated by polyclonal memory CD8 T cells that persist following infections for protection upon repeat exposure. Memory T cells can be triggered via T cell receptor recognition of their cognate antigen upon re-infection to exert effector functions, including cytotoxicity and cytokine production, and assist in pathogen elimination.<\/jats:p>\n                <jats:p>Alternatively, some T cells are \u2018bystander activated\u2019 by cytokines without an antigenic signal. This layered approach boosts efacient pathogen clearance but also poses a threat to host tissues if this response is not properly controlled. Here, we investigate the regulatory mechanisms modulating the tissue memory CD8 T cell response upon recall, leveraging viral rechallenge mouse models to distinguish antigen-driven versus cytokine-activated memory tissue CD8 T cell immunity. We and that regulatory T cells (Treg) participate in restricting cytotoxic and bystander activity without compromising the antigen-driven protective memory CD8 T cell response in mucosal T cells. Critically, Treg provide extrinsic regulation of tissue CD8 T cell cytotoxicity in part through restriction of available IL-2 and IL-15 trans-presentation. Our andings help deane the extrinsic environmental and cellular cues in mucosal tissues that direct tissue-memory CD8 T cells.<\/jats:p>","DOI":"10.64898\/2026.02.25.708034","type":"posted-content","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:00:58Z","timestamp":1772226058000},"source":"Crossref","is-referenced-by-count":0,"title":["Regulatory T cells restrain cytotoxic and bystander CD8 T cells without compromising antigen-driven memory in mucosal tissue"],"prefix":"10.64898","author":[{"given":"Irene Cruz","family":"Talavera","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"},{"name":"Department of Global Health, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica B.","family":"Graham","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Swarts","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna R.","family":"Traxinger","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"},{"name":"Department of Global Health, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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