KIR <sup>+</sup> CD8 <sup>+</sup> T cells suppress pathogenic T cells and are 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, Jun Li, Xuhuai Ji, Julie Wilhelmy, Alana M. McSween, Brad A. Palanski, Vamsee Mallajosyula, Nathan A. Bracey, Gopal Krishna Dhondalay, Kartik Bhamidipati, Joy A. Pai, Lucas Kipp, Jeffrey 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 Fernandez‐Becker, Kari C. Nadeau, Naresha Saligrama, Mark M. Davis
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.