{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:53:06Z","timestamp":1789678386570,"version":"4.0.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K19668, 17H05082, 19K22624, 20H03665, 21K18272, 21K07084, 19K08402, 21H02905, 20H00536"],"award-info":[{"award-number":["17K19668, 17H05082, 19K22624, 20H03665, 21K18272, 21K07084, 19K08402, 21H02905, 20H00536"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19ek0109214, 21gm1510002h001"],"award-info":[{"award-number":["19ek0109214, 21gm1510002h001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001695","name":"Japan Science and Technology Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007467","name":"School of Medicine, Keio University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007467","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015542","name":"GlaxoSmithKline Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Cytotoxic CD4<jats:sup>+<\/jats:sup> T cells (CD4-CTLs) show the presence of cytolytic granules, which include the enzymes granzyme and perforin. The cells have a pathogenic and protective role in various diseases, including cancer, viral infection, and autoimmune disease. In mice, cytotoxic CD4<jats:sup>+<\/jats:sup> T cells express CD8\u03b1\u03b1<jats:sup>+<\/jats:sup> and reside in the intestine (mouse CD4<jats:sup>+<\/jats:sup>CTLs; mCD4-CTLs). The population of cytotoxic CD4<jats:sup>+<\/jats:sup> T cells in the human intestine is currently unknown. Moreover, it is unclear how cytotoxic CD4 T cells change in patients with inflammatory bowel disease (IBD). Here, we aimed to identify cytotoxic CD4<jats:sup>+<\/jats:sup> T cells in the human intestine and analyze the characteristics of the population in patients with IBD using single-cell RNA-seq (scRNA-seq). In CD4<jats:sup>+<\/jats:sup> T cells, granzyme and perforin expression was high in humanMAIT (hMAIT) cells and hCD4<jats:sup>+<\/jats:sup>CD8A<jats:sup>+<\/jats:sup> T cell cluster. Both CD4 and CD8A were expressed in hTreg, hMAIT, and hCD4<jats:sup>+<\/jats:sup>CD8A<jats:sup>+<\/jats:sup> T cell clusters. Next we performed fast gene set enrichment analysis to identify cell populations that showed homology to mCD4CTLs. The analysis identified the hCD4<jats:sup>+<\/jats:sup>CD8A<jats:sup>+<\/jats:sup> T cell cluster (hCTL-like population; hCD4-CTL) similar to mouse CTLs. The percentage of CD4<jats:sup>+<\/jats:sup>CD8A<jats:sup>+<\/jats:sup> T cells among the total CD4<jats:sup>+<\/jats:sup> T cells in the inflamed intestine of the patients with Crohn\u2019s disease was significantly reduced compared with that in the noninflamed intestine of the patients. In summary, we identified cytotoxic CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells in the small intestine of humans. The integration of the mouse and human sc-RNA-seq data analysis highlight an approach to identify human cell populations related to mouse cell populations, which may help determine the functional properties of several human cell populations in mice.<\/jats:p>","DOI":"10.3389\/fimmu.2022.977117","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T14:40:00Z","timestamp":1666622400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Single-cell transcriptomics of human gut T cells identifies cytotoxic CD4+CD8A+ T cells related to mouse CD4 cytotoxic T 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