{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:02:20Z","timestamp":1793822540473,"version":"4.6.1"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"crossref","award":["P01-AI123086"],"award-info":[{"award-number":["P01-AI123086"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005294","name":"Massachusetts General Hospital","doi-asserted-by":"crossref","award":["the Patricia K. Donahoe,MD,Surgeon-Scientist Research Program Incubator Award"],"award-info":[{"award-number":["the Patricia K. Donahoe,MD,Surgeon-Scientist Research Program Incubator Award"]}],"id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018662","name":"Mitsukoshi Health and Welfare Foundation","doi-asserted-by":"crossref","award":["Research fellowship"],"award-info":[{"award-number":["Research fellowship"]}],"id":[{"id":"10.13039\/100018662","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"crossref","award":["Research fellowship"],"award-info":[{"award-number":["Research fellowship"]}],"id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,15]]},"abstract":"<jats:p>\n                    Tolerance of mouse kidney allografts arises in grafts that develop regulatory tertiary lymphoid organs (rTLOs). Single-cell RNA-seq (scRNA-seq) data and adoptive transfer of alloreactive T cells after transplantation showed that cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells are reprogrammed within the accepted graft to an exhausted\/regulatory-like phenotype mediated by IFN-\u03b3. Establishment of rTLOs was required because adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite the presence of intragraft CD8\n                    <jats:sup>+<\/jats:sup>\n                    cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance since renal allotransplantation into CD8-KO recipients resulted in acceptance and not rejection. Analysis of scRNA-seq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters and trajectory analysis showed that cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells are reprogrammed into an exhausted\/regulatory-like phenotype intratumorally. Induction of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call \u201cdefensive tolerance.\u201d This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.\n                  <\/jats:p>","DOI":"10.1172\/jci179709","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T12:01:24Z","timestamp":1718712084000},"source":"Crossref","is-referenced-by-count":23,"title":["Dysfunction of infiltrating cytotoxic CD8+ T cells within the graft promotes murine kidney allotransplant tolerance"],"prefix":"10.1172","volume":"134","author":[{"given":"Takahiro","family":"Yokose","sequence":"first","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery and"},{"name":"Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward S.","family":"Szuter","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery and"},{"name":"Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-3202","authenticated-orcid":true,"given":"Ivy","family":"Rosales","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery and"},{"name":"Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Guinn","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery and"},{"name":"Michael E. 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