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Human KIR + CD8 + T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19

Jing Li et al. bioRxiv. .

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  • KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19.
    Li J, Zaslavsky M, Su Y, Guo J, Sikora MJ, van Unen V, Christophersen A, Chiou SH, Chen L, Li J, Ji X, Wilhelmy J, McSween AM, Palanski BA, Mallajosyula VVA, Bracey NA, Dhondalay GKR, Bhamidipati K, Pai J, Kipp LB, Dunn JE, Hauser SL, Oksenberg JR, Satpathy AT, Robinson WH, Dekker CL, Steinmetz LM, Khosla C, Utz PJ, Sollid LM, Chien YH, Heath JR, Fernandez-Becker NQ, Nadeau KC, Saligrama N, Davis MM. Li J, et al. Science. 2022 Apr 15;376(6590):eabi9591. doi: 10.1126/science.abi9591. Epub 2022 Apr 15. Science. 2022. PMID: 35258337 Free PMC article.

Abstract

Previous reports show that Ly49 + CD8 + T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8 + T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various autoimmune diseases. Moreover, KIR + CD8 + T cells can efficiently eliminate pathogenic gliadin-specific CD4 + T cells from Celiac disease (CeD) patients' leukocytes in vitro . Furthermore, we observe elevated levels of KIR + CD8 + T cells, but not CD4 + regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Expanded KIR + CD8 + T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8 + T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells.

One-sentence summary: Here we identified KIR + CD8 + T cells as a regulatory CD8 + T cell subset in humans that suppresses self-reactive or otherwise pathogenic CD4 + T cells.

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