{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:05Z","timestamp":1792790405477,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Immunology","reference-count":19,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"American Heart Association","award":["26CDA1592374"],"award-info":[{"award-number":["26CDA1592374"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"award":["Sarnoff Foundation Scholar Career Development Award"],"award-info":[{"award-number":["Sarnoff Foundation Scholar Career Development Award"]}],"id":[{"id":"https:\/\/ror.org\/04csczr47","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Physician Scientist Fellowship Program"],"award-info":[{"award-number":["Physician Scientist Fellowship Program"]}],"id":[{"id":"https:\/\/ror.org\/00knt4f32","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institutes of Health","award":["K08HL181180"],"award-info":[{"award-number":["K08HL181180"]}]},{"name":"National Institutes of Health","award":["R01HL15590"],"award-info":[{"award-number":["R01HL15590"]}]},{"name":"National Institutes of Health","award":["R01HL156021"],"award-info":[{"award-number":["R01HL156021"]}]},{"name":"National Institutes of Health","award":["R01HL160688"],"award-info":[{"award-number":["R01HL160688"]}]},{"name":"National Institutes of Health","award":["R01HL170038"],"award-info":[{"award-number":["R01HL170038"]}]},{"name":"National Institutes of Health","award":["P01HL141084"],"award-info":[{"award-number":["P01HL141084"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Inflammatory T-cell infiltration is widely considered a hallmark of cardiac immune-mediated tissue injury, yet whether inflammation alone is sufficient to cause cardiac damage remains unclear. Using a spontaneous genetic model of immune checkpoint inhibitor myocarditis, we show that cardiac immune infiltration and tissue injury are separable processes. CD4\n                  <jats:sup>+<\/jats:sup>\n                  T-cells promote disease by licensing pathogenic CD8\n                  <jats:sup>+<\/jats:sup>\n                  T-cell responses through CD40L signaling, whereas perforin-dependent CD8\n                  <jats:sup>+<\/jats:sup>\n                  cytotoxicity is specifically required to induce cardiomyocyte death and cardiac arrhythmias. Loss of perforin prevented cardiac injury and rescued survival despite persistent myocardial inflammation, demonstrating that inflammatory infiltration is insufficient to produce lethal myocarditis in the absence of a cytotoxic effector program. CD40L blockade similarly attenuated pathogenic CD8\n                  <jats:sup>+<\/jats:sup>\n                  T-cell activation, myocardial inflammation, and mortality. These findings identify a cooperative CD4\u2013CD8 T-cell circuit that governs autoimmune cardiac injury and establish that acquisition of cytotoxic effector function, rather than inflammation alone, determines the transition from immune infiltration to tissue destruction.\n                <\/jats:p>","DOI":"10.64898\/2026.09.18.751575","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:50:12Z","timestamp":1790286612000},"source":"Crossref","is-referenced-by-count":0,"title":["A CD4-CD8 T-cell circuit converts cardiac inflammation into tissue injury"],"prefix":"10.64898","author":[{"given":"Amir Z.","family":"Munir","sequence":"first","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA"},{"name":"Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cade J.","family":"Krawiec","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riad","family":"Ghandour","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Baylis","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anya C.","family":"Shyani","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Ortega-Sollero","sequence":"additional","affiliation":[{"name":"Spanish National Cardiovascular Research Centre (CNIC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Nene","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA"},{"name":"Department of Medicine, University of California San Francisco, School of Medicine, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javid J.","family":"Moslehi","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, 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