{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:51:13Z","timestamp":1787010673528,"version":"build-2736575974"},"posted":{"date-parts":[[2025,9,18]]},"group-title":"Immunology","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"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":["U01 AI150741"],"award-info":[{"award-number":["U01 AI150741"]}],"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":["R01 AI177377"],"award-info":[{"award-number":["R01 AI177377"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Gates Foundation","award":["OPP 1113682"],"award-info":[{"award-number":["OPP 1113682"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  (\n                  <jats:italic>Pf<\/jats:italic>\n                  ) induces the clonal expansion of antigen-specific type 1 regulatory T (Tr1) cells with a capacity for long-term memory. Tr1 cells comprise nearly 90% of the\n                  <jats:italic>Pf<\/jats:italic>\n                  blood stage antigen-specific CD4+ T cell pool in children. Though, whether Tr1 cells contribute to protection from malaria remains undetermined. To address this critical gap in knowledge, we first performed scRNAseq on gated cell populations to validate CXCR6+ CD127- as new phenotypic markers to enrich for bona-fide Tr1 cells. Importantly, these Tr1 cells potently suppressed the proliferation of other CD4+ T cells\n                  <jats:italic>in vitro<\/jats:italic>\n                  via IL-10 secretion. Among children living in malaria-endemic Uganda, CXCR6+ CD127- Tr1 cells were the dominant responding subset to\n                  <jats:italic>Pf<\/jats:italic>\n                  -infected red blood cell stimulation\n                  <jats:italic>in vitro<\/jats:italic>\n                  . They also rapidly expanded following malaria and expressed IL-10 and IFNg during infection\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Tr1 abundance correlated with plasma concentrations of granzyme A, IFNg, IL-10, and LAG3, suggesting that these cells act systemically. Higher CXCR6+ CD127- Tr1 cell frequencies correlated with a lower probability of symptoms given parasitemia but were also associated with delayed parasite clearance among untreated, asymptomatic children. These data suggest that Tr1 cells help mediate clinical immunity to malaria but may also facilitate parasite persistence through mechanisms of immune regulation.\n                <\/jats:p>","DOI":"10.1101\/2025.09.16.676649","type":"posted-content","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T05:30:24Z","timestamp":1758259824000},"source":"Crossref","is-referenced-by-count":3,"title":["CXCR6\u207a CD127\u207b Tr1 Cells Balance Immunity and Persistence in Plasmodium falciparum 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