{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:55:13Z","timestamp":1783702513922,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T00:00:00Z","timestamp":1733616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100015581","name":"Houston Methodist Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Chronic T cell receptor (TCR) signalling induces T cell exhaustion, characterised by reduced capacity to induce tissue damage. Here, we investigated the therapeutic potential of the anti\u2010TCR\u03b2 (H57\u2010597) monoclonal antibody (mAb) in a mouse model of SLE. Four\u2010month\u2010old MRL\/<jats:italic>lpr<\/jats:italic> mice exhibiting SLE phenotypes received 5 weekly doses of anti\u2010TCR\u03b2 mAb or phosphate\u2010buffered saline (PBS) vehicle control. Subsequently, mouse survival was monitored daily. On day 1 post the final dose of treatment, SLE pathogenesis was determined using histological staining and spot urine test. T and B cell states in the brain, kidney, and secondary lymphoid organs were determined by flow cytometry. Transient treatment of anti\u2010TCR\u03b2 mAb significantly prolonged the survival of MRL\/<jats:italic>lpr<\/jats:italic> mice. Accordingly, MRL\/<jats:italic>lpr<\/jats:italic> mice in the anti\u2010TCR\u03b2 mAb group exhibited decreased proteinuria scores and minimal renal pathological damage compared to the PBS control group. Flow cytometric analysis revealed that anti\u2010TCR\u03b2 mAb treatment resulted in a reduction in the frequencies of CD4<jats:sup>+<\/jats:sup> T cells and CD138<jats:sup>+<\/jats:sup>B220<jats:sup>lo\/\u2212<\/jats:sup> plasma cells, plus an increase in Foxp3<jats:sup>+<\/jats:sup> regulatory T cell frequency. Furthermore, CD4<jats:sup>+<\/jats:sup> T cells from anti\u2010TCR\u03b2 mAb treated mice exhibited elevated expression levels of PD\u20101 and TIM\u20103, with reduced IFN\u2010\u03b3 production, indicative of an exhaustion\u2010like phenotype. Therefore, transient administration of anti\u2010TCR\u03b2 mAb treatment induces an exhaustion\u2010like phenotype in CD4<jats:sup>+<\/jats:sup> T cells, resulting in prolonged survival of MRL\/<jats:italic>lpr<\/jats:italic> mice. Inducing autoreactive T\u2010cell exhaustion holds promise as an attractive therapeutic approach for SLE.<\/jats:p>","DOI":"10.1111\/imm.13881","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T04:20:22Z","timestamp":1733718022000},"page":"239-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Transient Anti\u2010<scp>TCR\u03b2 mAb<\/scp> Treatment Induces <scp>CD4<\/scp><sup>+<\/sup><scp>T<\/scp> Cell Exhaustion and Prolongs Survival in a Mouse Model of Systemic Lupus Erythematosus"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0354-9598","authenticated-orcid":false,"given":"Nancy Mize","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Immunobiology &amp; Transplant Science Center, Department of Surgery Houston Methodist Research Institute, Houston Methodist Hospital  Houston Texas USA"},{"name":"College of Medicine Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-0280","authenticated-orcid":false,"given":"Dawei","family":"Zou","sequence":"additional","affiliation":[{"name":"Immunobiology &amp; Transplant Science Center, Department of Surgery Houston Methodist Research Institute, Houston Methodist Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihua","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine Houston Methodist Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances Xiuyan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Colorado Anschutz Medical Campus  Aurora Colorado 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