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[Preprint]. 2021 Dec 25:2021.12.23.473930. [Version 1] doi: 10.1101/2021.12.23.473930

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

Jing Li, Maxim Zaslavsky, Yapeng Su, Michael J Sikora, Vincent van Unen, Asbjørn Christophersen, Shin-Heng Chiou, Liang Chen, Jiefu Li, Xuhuai Ji, Julie Wilhelmy, Alana M McSween, Brad A Palanski, Venkata Vamsee Aditya Mallajosyula, Gopal Krishna R Dhondalay, Kartik Bhamidipati, Joy Pai, Lucas B Kipp, Jeffrey E Dunn, Stephen L Hauser, Jorge R Oksenberg, Ansuman T Satpathy, William H Robinson, Lars M Steinmetz, Chaitan Khosla, Paul J Utz, Ludvig M Sollid, James R Heath, Nielsen Q Fernandez-Becker, Kari C Nadeau, Naresha Saligrama, Mark M Davis
PMCID: PMC8722592  PMID: 34981055

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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