{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:33:52Z","timestamp":1788050032905,"version":"build-2784847793"},"reference-count":61,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"83","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,5,26]]},"abstract":"<jats:p>\n            After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8\n            <jats:sup>+<\/jats:sup>\n            tissue-resident memory T cells (T\n            <jats:sub>RM<\/jats:sub>\n            ), the developmental origins and transcriptional regulation of CD4\n            <jats:sup>+<\/jats:sup>\n            T\n            <jats:sub>RM<\/jats:sub>\n            remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4\n            <jats:sup>+<\/jats:sup>\n            T\n            <jats:sub>RM<\/jats:sub>\n            in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating T\n            <jats:sub>H<\/jats:sub>\n            1 and the progressive acquisition of a mature T\n            <jats:sub>RM<\/jats:sub>\n            program. Single-cell RNA sequencing identified heterogeneity among established CD4\n            <jats:sup>+<\/jats:sup>\n            T\n            <jats:sub>RM<\/jats:sub>\n            , which were predominantly located in the lamina propria, and revealed a population of cells that coexpressed both effector- and memory-associated genes, including the transcriptional regulators Blimp1, Id2, and Bcl6. T\n            <jats:sub>H<\/jats:sub>\n            1-associated Blimp1 and Id2 and T\n            <jats:sub>FH<\/jats:sub>\n            -associated Bcl6 were required for early T\n            <jats:sub>RM<\/jats:sub>\n            formation and development of a mature T\n            <jats:sub>RM<\/jats:sub>\n            population in the SI. These results demonstrate a developmental relationship between T\n            <jats:sub>H<\/jats:sub>\n            1 effector cells and the establishment of early T\n            <jats:sub>RM<\/jats:sub>\n            , as well as highlighted differences in CD4\n            <jats:sup>+<\/jats:sup>\n            versus CD8\n            <jats:sup>+<\/jats:sup>\n            T\n            <jats:sub>RM<\/jats:sub>\n            populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4\n            <jats:sup>+<\/jats:sup>\n            T\n            <jats:sub>RM<\/jats:sub>\n            in response to viral infection.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.abq7486","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T17:58:06Z","timestamp":1683914286000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":24,"title":["Transcriptional programming of CD4\n            <sup>+<\/sup>\n            T\n            <sub>RM<\/sub>\n            differentiation in viral infection balances effector- and memory-associated gene expression"],"prefix":"10.1126","volume":"8","author":[{"given":"Quynh P.","family":"Nguyen","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1990-155X","authenticated-orcid":true,"given":"Kennidy K.","family":"Takehara","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7795-350X","authenticated-orcid":true,"given":"Tianda Z.","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9594-1377","authenticated-orcid":true,"given":"Maximilian","family":"Heeg","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3675-048X","authenticated-orcid":true,"given":"Kyla D.","family":"Omilusik","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0752-2130","authenticated-orcid":true,"given":"J. Justin","family":"Milner","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3860-3491","authenticated-orcid":true,"given":"Sara","family":"Quon","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9688-0190","authenticated-orcid":true,"given":"Matthew E.","family":"Pipkin","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Scripps Research Institute, Jupiter, FL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2474-2837","authenticated-orcid":true,"given":"Jinyong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, College of Medicine, Catholic University of Korea, Seoul, South Korea."},{"name":"Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6484-6262","authenticated-orcid":true,"given":"Shane","family":"Crotty","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA."},{"name":"Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5900-508X","authenticated-orcid":true,"given":"Ananda W.","family":"Goldrath","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, 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