{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T18:17:21Z","timestamp":1783361841416,"version":"3.54.6"},"posted":{"date-parts":[[2026,7,1]]},"group-title":"Immunology","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The National Institute of Health","award":["1RO1DK132549"],"award-info":[{"award-number":["1RO1DK132549"]}]},{"name":"The National Institute of Health","award":["R01DK129343"],"award-info":[{"award-number":["R01DK129343"]}]},{"name":"The National Institute of Health","award":["R01DK141802"],"award-info":[{"award-number":["R01DK141802"]}]},{"DOI":"10.13039\/100014499","name":"Stanford Diabetes Research Center","doi-asserted-by":"crossref","award":["P30DK116074"],"award-info":[{"award-number":["P30DK116074"]}],"id":[{"id":"10.13039\/100014499","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Breakthrough T1D\/Northern California JDRF-COE","award":["11715sc"],"award-info":[{"award-number":["11715sc"]}]},{"name":"Ruth L. Kirschstein National Research Service Award","award":["DK007217-47"],"award-info":[{"award-number":["DK007217-47"]}]},{"name":"Ruth L. Kirschstein National Research Service Award","award":["DK007217-48"],"award-info":[{"award-number":["DK007217-48"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Type 1 diabetes (T1D) is caused by T cell-mediated autoimmune destruction of insulin-producing islet \u03b2-cells. Treatment with T-cell depleting therapies delays the progression of stage 2 and 3 T1D, but these agents exert broad immunosuppressive effects on T cell populations, including T regulatory cells (Tregs), which are key in promoting immune tolerance. We evaluated non-obese diabetic (NOD) mice and recently diagnosed T1D patients and identified CD38 as a marker for pathogenic T cell populations. Using adoptive T-cell transfer in Recombination Activating Gene 1 knockout NOD mice and in a humanized mouse model of autoimmune diabetes, we demonstrated that CD38-expressing autoreactive T cells drive diabetes pathogenesis. Furthermore, we found that selective depletion of CD38\n                  <jats:sup>+<\/jats:sup>\n                  cells, using an anti-CD38 monoclonal antibody (mAb), prevents insulitis and diabetes onset without depleting CD4\n                  <jats:sup>+<\/jats:sup>\n                  CD25\n                  <jats:sup>+<\/jats:sup>\n                  Tregs. Administration of anti-CD38 mAb did not adversely affect islet function and may selectively eliminate immunogenic senescent islet \u03b2-cells. These results support the strategy of selectively depleting diabetogenic T cells using an anti-CD38 mAb to treat T1D and restore immune tolerance. Therefore, transient depletion of autoreactive T cells using anti-CD38 mAb may provide a novel strategy to prevent or abrogate \u03b2-cell autoimmunity in T1D.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One sentence summary<\/jats:title>\n                  <jats:p>Pathogenic autoreactive are characterized by CD38 overexpression, and their selective depletion with anti-CD38 monoclonal antibody prevents autoimmune diabetes.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.27.734105","type":"posted-content","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:35:12Z","timestamp":1782959712000},"source":"Crossref","is-referenced-by-count":0,"title":["CD38 defines a therapeutically targetable pathogenic T cell population for precision immunotherapy in autoimmune diabetes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1275-8516","authenticated-orcid":false,"given":"Shiva","family":"Pathak","sequence":"first","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Stanford Diabetes Research Center, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Cellular Immune Tolerance Program, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwan","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Nagy","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Stanford Diabetes Research Center, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Cellular Immune Tolerance Program, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sooyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Stanford Diabetes Research Center, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Division of Endocrinology, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron S.","family":"Bader","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Cellular Immune Tolerance Program, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shobha","family":"Regmi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina P.","family":"Iliopoulou","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Cellular Immune Tolerance Program, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-I","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Cellular Immune Tolerance Program, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biki","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Villar-Prados","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine; 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Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avnesh S.","family":"Thakor","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent P.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Stanford Diabetes Research Center, Stanford University School of Medicine; Stanford, CA, USA"},{"name":"Cellular Immune Tolerance Program, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Utz","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Stanford University School of Medicine; Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine; 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