{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:10:42Z","timestamp":1793862642011,"version":"4.6.1"},"reference-count":47,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["R01 AI164716"],"award-info":[{"award-number":["R01 AI164716"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["K23 AI144036"],"award-info":[{"award-number":["K23 AI144036"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,8]]},"abstract":"<jats:p>\n                    While the inhibitory receptor Fc\u03b3RIIB has been shown to be upregulated on activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in both mice and humans, its effect on T cell fate during infection has not been fully elucidated. We identified an increase in Fc\u03b3RIIB-expressing CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in patients with COVID-19 relative to healthy controls as well as in mouse models of viral infection. Despite its well-known role as an Fc receptor, Fc\u03b3RIIB also ligates the immunosuppressive cytokine Fgl2, resulting in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell apoptosis. Both chronic LCMV infection in mice and COVID-19 in humans resulted in a significant increase in plasma Fgl2. Transfer of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells into a Fgl2-replete, but not Fgl2-devoid, environment resulted in elimination of Fc\u03b3RIIB\n                    <jats:sup>+<\/jats:sup>\n                    , but not Fc\u03b3RIIB\n                    <jats:sup>\u2013<\/jats:sup>\n                    , CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Similarly, plasma Fgl2 was directly proportional to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell lymphopenia in patients with COVID-19. RNA-Seq analysis demonstrated that\n                    <jats:italic>Fgl2<\/jats:italic>\n                    was produced by murine virus\u2013specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, with an increase in\n                    <jats:italic>Fgl2<\/jats:italic>\n                    in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells elicited during chronic versus acute viral infection.\n                    <jats:italic>Fgl2<\/jats:italic>\n                    was also upregulated in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from patients with COVID-19 versus healthy controls. In summary, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell production of Fgl2 during viral infection underpinned an Fc\u03b3RIIB-mediated loss of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell immunity in both mice and humans.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.186259","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T14:04:17Z","timestamp":1744034657000},"source":"Crossref","is-referenced-by-count":4,"title":["Fgl2 regulates Fc\u03b3RIIB+CD8+ T cell responses during infection"],"prefix":"10.1172","volume":"10","author":[{"given":"Anna B.","family":"Morris","sequence":"first","affiliation":[{"name":"Department of Surgery and Emory Transplant Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max W.","family":"Adelman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Emory University, 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