RT Journal Article
SR Electronic
T1 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
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.23.473930
DO 10.1101/2021.12.23.473930
A1 Jing Li
A1 Maxim Zaslavsky
A1 Yapeng Su
A1 Michael J. Sikora
A1 Vincent van Unen
A1 Asbjørn Christophersen
A1 Shin-Heng Chiou
A1 Liang Chen
A1 Jiefu Li
A1 Xuhuai Ji
A1 Julie Wilhelmy
A1 Alana M. McSween
A1 Brad A. Palanski
A1 Venkata Vamsee Aditya Mallajosyula
A1 Gopal Krishna R. Dhondalay
A1 Kartik Bhamidipati
A1 Joy Pai
A1 Lucas B. Kipp
A1 Jeffrey E. Dunn
A1 Stephen L. Hauser
A1 Jorge R. Oksenberg
A1 Ansuman T. Satpathy
A1 William H. Robinson
A1 Lars M. Steinmetz
A1 Chaitan Khosla
A1 Paul J. Utz
A1 Ludvig M. Sollid
A1 James R. Heath
A1 Nielsen Q. Fernandez-Becker
A1 Kari C. Nadeau
A1 Naresha Saligrama
A1 Mark M. Davis
YR 2021
UL http://biorxiv.org/content/early/2021/12/25/2021.12.23.473930.abstract
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.