{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T11:43:35Z","timestamp":1792928615715,"version":"4.5.0"},"reference-count":60,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["RO1 AI40459"],"award-info":[{"award-number":["RO1 AI40459"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["U01 AI063594"],"award-info":[{"award-number":["U01 AI063594"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["RO1-AI113142"],"award-info":[{"award-number":["RO1-AI113142"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,15]]},"abstract":"<jats:p>\n                    Virus-induced memory T cells often express functional cross-reactivity, or heterologous immunity, to other viruses and to allogeneic MHC molecules that is an important component of pathogenic responses to allogeneic transplants. During immune responses, antigen-reactive naive and central memory T cells proliferate in secondary lymphoid organs to achieve sufficient cell numbers to effectively respond, whereas effector memory T cell proliferation occurs directly within the peripheral inflammatory microenvironment. Mechanisms driving heterologous memory T cell proliferation and effector function expression within peripheral tissues remain poorly understood. Here, we dissected proliferation of heterologous donor-reactive memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and their effector functions following infiltration into heart allografts with low or high intensities of ischemic inflammation. Proliferation within both ischemic conditions required p40 homodimer\u2013induced IL-15 transpresentation by graft DCs, but expression of effector functions mediating acute allograft injury occurred only in high-ischemic allografts. Transcriptional responses of heterologous donor-reactive memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells were distinct from donor antigen\u2013primed memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells during early activation in allografts and at graft rejection. Overall, the results provide insights into mechanisms driving heterologous effector memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell proliferation and the separation between proliferation and effector function that is dependent on the intensity of inflammation within the tissue microenvironment.\n                  <\/jats:p>","DOI":"10.1172\/jci172760","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T12:00:28Z","timestamp":1706184028000},"source":"Crossref","is-referenced-by-count":3,"title":["p40 homodimers bridge ischemic tissue inflammation and heterologous alloimmunity in mice via IL-15 transpresentation"],"prefix":"10.1172","volume":"134","author":[{"given":"Hidetoshi","family":"Tsuda","sequence":"first","affiliation":[{"name":"Department of Inflammation & Immunity, Lerner Research Institute, Cleveland, Ohio, USA."},{"name":"Transplant Center, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8609-4797","authenticated-orcid":true,"given":"Karen S.","family":"Keslar","sequence":"additional","affiliation":[{"name":"Department of Inflammation & Immunity, Lerner Research Institute, Cleveland, Ohio, USA."},{"name":"Transplant Center, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-1827","authenticated-orcid":true,"suffix":"III","given":"William M.","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Department of Inflammation & Immunity, Lerner Research Institute, Cleveland, Ohio, USA."},{"name":"Transplant Center, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4673-6913","authenticated-orcid":true,"given":"Peter 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