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In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike \u03b1\u03b2-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted \u03b3\u03b4-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFN\u03b3-producing \u03b3\u03b4 T cells. We found that CD27\n                    <jats:sup>+<\/jats:sup>\n                    Ly6C\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells convert into CD27\n                    <jats:sup>+<\/jats:sup>\n                    Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    cells, and these CD27\n                    <jats:sup>+<\/jats:sup>\n                    Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    cells control cancer progression in mice, while the CD27\n                    <jats:sup>+<\/jats:sup>\n                    Ly6C\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature \u03b3\u03b4-T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27\n                    <jats:sup>+<\/jats:sup>\n                    Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    cells and human V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    cells, while IL-27 is dispensable for mouse CD27\n                    <jats:sup>+<\/jats:sup>\n                    Ly6C\n                    <jats:sup>\u2212<\/jats:sup>\n                    cell and human V\u03b41\n                    <jats:sup>+<\/jats:sup>\n                    cell functions. These data reveal increased complexity within IFN\u03b3-producing \u03b3\u03b4-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology.\n                  <\/jats:p>","DOI":"10.1038\/s44318-024-00133-1","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T12:02:03Z","timestamp":1717070523000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["IL-27 maintains cytotoxic Ly6C+ \u03b3\u03b4 T cells that arise from immature precursors"],"prefix":"10.1038","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-4413","authenticated-orcid":false,"given":"Robert","family":"Wiesheu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah 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