PT  - JOURNAL ARTICLE
AU  - Jing Li
AU  - Maxim Zaslavsky
AU  - Yapeng Su
AU  - Michael J. Sikora
AU  - Vincent van Unen
AU  - Asbjørn Christophersen
AU  - Shin-Heng Chiou
AU  - Liang Chen
AU  - Jiefu Li
AU  - Xuhuai Ji
AU  - Julie Wilhelmy
AU  - Alana M. McSween
AU  - Brad A. Palanski
AU  - Venkata Vamsee Aditya Mallajosyula
AU  - Gopal Krishna R. Dhondalay
AU  - Kartik Bhamidipati
AU  - Joy Pai
AU  - Lucas B. Kipp
AU  - Jeffrey E. Dunn
AU  - Stephen L. Hauser
AU  - Jorge R. Oksenberg
AU  - Ansuman T. Satpathy
AU  - William H. Robinson
AU  - Lars M. Steinmetz
AU  - Chaitan Khosla
AU  - Paul J. Utz
AU  - Ludvig M. Sollid
AU  - James R. Heath
AU  - Nielsen Q. Fernandez-Becker
AU  - Kari C. Nadeau
AU  - Naresha Saligrama
AU  - Mark M. Davis
TI  - Human KIR<sup>+</sup>CD8<sup>+</sup> T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19
AID  - 10.1101/2021.12.23.473930
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.12.23.473930
4099  - http://biorxiv.org/content/early/2021/12/25/2021.12.23.473930.short
4100  - http://biorxiv.org/content/early/2021/12/25/2021.12.23.473930.full
AB  - 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.Competing Interest StatementN.S., M.M.D. and J.L. are co-inventors on patent application 62/882,810, which includes discoveries described in this manuscript. M.M.D. is involved in a start-up company for the clinical applications of these discoveries. Other co-authors declare that they have no competing interests.