The detailed characterization of human γδ 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 γδ T cells and a robust mapping method for additional γδ T lymphocytes. Here, we incepted such a method to characterize thousands of γδ 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 γδ tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRVγ9 and TCRVγnon9 subsets of γδ 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 γδ T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes γδ T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar γδ T cell lymphopenia to that seen in adult patients. However, blood γδ 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 γδ T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors.
【저자키워드】 COVID-19, Transcriptome, Tumor, Human, lymphocyte, trajectory, Single Cell, differentiation, gammadelta, 【초록키워드】 coronavirus disease, therapy, pediatric, children, memory, COVID-19 disease, Peripheral blood, T cell, lymphoma, Patient, PBMC, T lymphocytes, recruitment, disease, patients, single-cell, severe COVID-19 disease, Blood, T cell activation, Inflammatory, tumors, cancer patient, lung lesion, mononuclear cell, Patients with cancer, Pediatric patient, tissue, syndrome, T lymphocyte, lung tissue, acute COVID-19, T cell lymphopenia, scRNAseq, transcriptomic, Cell, robust, healthy, increase, promote, subset, patients with COVID-19, 【제목키워드】 RNAseq, Profiling,