KIR+CD8+ T cells suppress pathogenic T cells and ar active in autoimmune diseases and COVID-19

Jing Li, Maxim Zaslavsky, Yapeng Su, Jing Guo, 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, Nathan A. Bracey, Gopal Krishna R. Dhondalay, Kartik Bhamidipati, Joy Pai, Lucas B. KippJeffrey E. Dunn, Stephen L. Hauser, Jorge R. Oksenberg, Ansuman T. Satpathy, William H. Robinson, Cornelia L. Dekker, Lars M. Steinmetz, Chaitan Khosla, Paul J. Utz, Ludvig M. Sollid, Yueh Hsiu Chien, James R. Heath, Nielsen Q. Fernandez-Becker, Kari C. Nadeau, Naresha Saligrama, Mark M. Davis

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

In this work, we find that CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49+CD8+ regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8+ T cells efficiently eliminated pathogenic gliadin-specific CD4+ T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49+CD8+ T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8+ T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases.

Original languageEnglish
Article numbereabi9591
JournalScience
Volume376
Issue number6590
DOIs
StatePublished - Apr 15 2022

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