| First Author | Wiesheu R | Year | 2024 |
| Journal | EMBO J | Volume | 43 |
| Issue | 14 | Pages | 2878-2907 |
| PubMed ID | 38816652 | Mgi Jnum | J:357390 |
| Mgi Id | MGI:7703061 | Doi | 10.1038/s44318-024-00133-1 |
| Citation | Wiesheu R, et al. (2024) IL-27 maintains cytotoxic Ly6C(+) gammadelta T cells that arise from immature precursors. EMBO J 43(14):2878-2907 |
| abstractText | In mice, gammadelta-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNgamma-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike alphabeta-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted gammadelta-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNgamma-producing gammadelta T cells. We found that CD27(+) Ly6C(-) cells convert into CD27(+)Ly6C(+) cells, and these CD27(+)Ly6C(+) cells control cancer progression in mice, while the CD27(+)Ly6C(-) cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature gammadelta-T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27(+)Ly6C(+) cells and human Vdelta2(+) cells, while IL-27 is dispensable for mouse CD27(+)Ly6C(-) cell and human Vdelta1(+) cell functions. These data reveal increased complexity within IFNgamma-producing gammadelta-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology. |
