{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:28:14Z","timestamp":1784824094087,"version":"3.55.0"},"reference-count":59,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"crossref","award":["N.A."],"award-info":[{"award-number":["N.A."]}],"id":[{"id":"10.13039\/501100012351","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,24]]},"abstract":"<jats:p>\n                    Peripheral helper T (Tph) and follicular helper T (Tfh) cells are key regulators of B cell differentiation and antibody production, making them promising targets for autoimmune disease treatment. However, their differentiation mechanisms differ significantly between humans and mice, limiting drug validation in mouse models. Here, we present a simple and effective method for in vivo proliferation of human Tph\/Tfh and B cells. We discovered that after depleting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells of human peripheral blood mononuclear cell\u2013transferred immunodeficient mice (CD8T\u0394hPBMC mice), human Tph\/Tfh cells and B cells proliferated markedly in the spleen compared with those in human PBMC\u2013transferred immunodeficient mice (hPBMC mice). Transcriptome analysis confirmed proliferating cells\u2019 close resemblance to human Tph\/Tfh cells. Furthermore, multicolor flow cytometry revealed CXCL13\n                    <jats:sup>+<\/jats:sup>\n                    Tph cells infiltrating Sj\u00f6gren\u2019s syndrome\u2013associated (SjS-associated) organs, such as salivary glands. Single-cell RNA sequencing identified IL-21\n                    <jats:sup>+<\/jats:sup>\n                    CXCL13\n                    <jats:sup>+<\/jats:sup>\n                    IFN-\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    ICOS\n                    <jats:sup>+<\/jats:sup>\n                    TIGIT\n                    <jats:sup>+<\/jats:sup>\n                    GPR56\n                    <jats:sup>+<\/jats:sup>\n                    Tph cells in the salivary glands. These findings are consistent with reduced saliva volume and elevated SjS markers, such as anti-SSA antibody, in these mice, which were both ameliorated by immunosuppressants. In vitro, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from hPBMC mice induced B cell apoptosis and inhibited Tph\/Tfh differentiation. This model advances understanding of human Tph\/Tfh cell biology and offers a valuable platform for studying SjS and therapeutic targets.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.191700","type":"journal-article","created":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T19:00:41Z","timestamp":1763924441000},"source":"Crossref","is-referenced-by-count":4,"title":["CD8+ T cell depletion promotes human Tph\/Tfh cell proliferation and Sj\u00f6gren syndrome\u2013like symptoms in PBMC-based humanized 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