Cerapio J. P. auteur aut IRD Perrier M. auteur aut IRD Pont F. auteur aut IRD Tosolini M. auteur aut IRD Laurent C. auteur aut IRD Bertani Stéphane auteur aut IRD Fournie J. J. auteur aut IRD text journalArticle eng text/pdf reformatted digital access The detailed characterization of human gamma delta T lymphocyte differentiation at the single-cell transcriptomic (scRNAseq) level in tumors and patients with coronavirus disease 2019 (COVID-19) requires both a reference differentiation trajectory of gamma delta T cells and a robust mapping method for additional gamma delta T lymphocytes. Here, we incepted such a method to characterize thousands of gamma delta T lymphocytes from (n = 95) patients with cancer or adult and pediatric COVID-19 disease. We found that cancer patients with human papillomavirus-positive head and neck squamous cell carcinoma and Epstein-Barr virus-positive Hodgkin's lymphoma have gamma delta tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRV gamma 9 and TCRV gamma non9 subsets of gamma delta T lymphocytes relocalize from peripheral blood mononuclear cells (PBMC) to the infected lung tissue, where their advanced differentiation, tissue residency, and exhaustion reflect T cell activation. Although severe COVID-19 disease increases both recruitment and exhaustion of gamma delta T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes gamma delta T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar gamma delta T cell lymphopenia to that seen in adult patients. However, blood gamma delta T cells from children with the COVID-19-related multisystem inflammatory syndrome are not lymphodepleted, but they are differentiated as in healthy PBMC. These findings suggest that some virus-induced memory gamma delta T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors. specialized human gammadelta lymphocyte tumor COVID-19 transcriptome single cell differentiation trajectory 050 052 020 13 11 2212 [14 p.] 2021 https://www.documentation.ird.fr/hor/fdi:010083797 10.3390/v13112212 [F B010083797] https://www.documentation.ird.fr/hor/fdi:010083797 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2022-01/010083797.pdf IRD - Base Horizon / Pleins textes 2022-01-12 2025-02-24 fdi:010083797 fre