{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:29:50Z","timestamp":1793212190177,"version":"4.5.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 HL143349"],"award-info":[{"award-number":["R01 HL143349"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32 AI089443"],"award-info":[{"award-number":["T32 AI089443"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,8]]},"abstract":"<jats:p>\n                    In allogeneic hematopoietic transplantation, donor \u03b1\u03b2 T cells attack recipient tissues, causing graft versus host disease (GVHD). A longstanding question has been how GVHD is maintained despite T cell exhaustion from chronic alloantigen stimulation. In other exhaustion models, CD8 responses are sustained by CD39\n                    <jats:sup>lo<\/jats:sup>\n                    Tim-3\n                    <jats:sup>lo<\/jats:sup>\n                    Tox\n                    <jats:sup>hi<\/jats:sup>\n                    TCF-1\n                    <jats:sup>hi<\/jats:sup>\n                    precursor exhausted T cells (T\n                    <jats:sub>PEX<\/jats:sub>\n                    ). Here we characterize CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>PEX<\/jats:sub>\n                    in the B6(H-2\n                    <jats:sup>b<\/jats:sup>\n                    )\u2192129(H-2\n                    <jats:sup>b<\/jats:sup>\n                    ) GVHD model wherein responses against the minor histocompatibility antigen H60 can be tracked using MHCI-tetramers (Tet\n                    <jats:sup>H60<\/jats:sup>\n                    ). Early after transplant, Tet\n                    <jats:sup>H60+<\/jats:sup>\n                    CD8 cells were uniformly PD-1\n                    <jats:sup>hi<\/jats:sup>\n                    Tox\n                    <jats:sup>hi<\/jats:sup>\n                    , whereas Tet\n                    <jats:sup>H60\u2013<\/jats:sup>\n                    cells also had PD-1\n                    <jats:sup>lo<\/jats:sup>\n                    Tox\n                    <jats:sup>lo<\/jats:sup>\n                    cells, indicative of more diverse antigen experiences. Among Tet\n                    <jats:sup>H60+<\/jats:sup>\n                    and Tet\n                    <jats:sup>H60\u2013<\/jats:sup>\n                    populations were CD39\n                    <jats:sup>lo<\/jats:sup>\n                    TCF-1\n                    <jats:sup>hi<\/jats:sup>\n                    cells. Upon competitive retransplantation, Tet\n                    <jats:sup>H60+<\/jats:sup>\n                    CD39\n                    <jats:sup>lo<\/jats:sup>\n                    TCF-1\n                    <jats:sup>hi<\/jats:sup>\n                    cells outcompeted Tet\n                    <jats:sup>H60+<\/jats:sup>\n                    CD39\n                    <jats:sup>hi<\/jats:sup>\n                    TCF-1\n                    <jats:sup>lo<\/jats:sup>\n                    cells and underwent self-renewal, whereas CD39\n                    <jats:sup>hi<\/jats:sup>\n                    TCF-1\n                    <jats:sup>lo<\/jats:sup>\n                    cells did not yield TCF-1\n                    <jats:sup>hi<\/jats:sup>\n                    cells. To test the role of TCF-1, we studied CD8 cells lacking long TCF-1 isoforms (\n                    <jats:italic>\n                      p45\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ).\n                    <jats:italic>\n                      P45\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    cells were outcompeted by WT cells when transplanted into 129 recipients, though they expanded similarly in syngeneic recipients. In the B6\u2192C3H.SW(H-2\n                    <jats:sup>b<\/jats:sup>\n                    ) model,\n                    <jats:italic>\n                      p45\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    CD8 cells caused less weight loss than did WT CD8 cells; however, histopathologic GVHD was similar in both groups.\n                    <jats:italic>\n                      P45\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    and WT CD8 cells also had similar graft versus leukemia activity. These results highlight the complex biology of TCF-1 in supporting alloreactive T cell function.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.181568","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T18:17:50Z","timestamp":1759861070000},"source":"Crossref","is-referenced-by-count":6,"title":["The role of TCF-1+CD8+ exhausted progenitors and TCF-1 in graft-versus-host responses"],"prefix":"10.1172","volume":"10","author":[{"given":"Kevin","family":"Quann","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Malignant Hematology and Medical Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faruk","family":"Sacirbegovic","sequence":"additional","affiliation":[{"name":"Starzl Transplantation Institute, University of Pittsburgh\/University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 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