Journal
VIRUSES-BASEL
Volume 13, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/v13112212
Keywords
human; gammadelta; lymphocyte; tumor; COVID-19; transcriptome; single cell; differentiation; trajectory
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Universite Toulouse 3-Paul Sabatier (UPS)
- Centre National de la Recherche Scientifique (CNRS)
- Laboratoire dExcellence Toulouse Cancer (TOUCAN-2) [ANR11-LABX]
- Fondation ARC [PGA1-RF2019-0208691]
- Institut Universitaire du Cancer de Toulouse-Oncopole under contract CIEL
- Institut Carnot Lymphome under contract CALYM
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The study characterized the differentiation of human gamma delta T lymphocytes in tumors and COVID-19 patients at the single-cell transcriptomic level. It found that tumor-infiltrating gamma delta T cells in certain cancer patients were more likely to recirculate and avoid exhaustion, while in COVID-19 patients, gamma delta T cells relocated to infected lung tissue displaying different differentiation, tissue residency, and exhaustion patterns.
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.
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