KIR + CD8 + T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19
covid-19; washington; seattle; isb; Animals; Autoimmune Diseases; CD8-Positive T-Lymphocytes; COVID-19; Humans; Mice; Receptors, KIR; T-Lymphocytes, Regulatory
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.
Institute for Systems Biology
Li, Jing; Zaslavsky, Maxim; Su, Yapeng; Guo, Jing; Sikora, Michael J; van Unen, Vincent; Christophersen, Asbjørn; Chiou, Shin-Heng; Chen, Liang; Li, Jiefu; Ji, Xuhuai; Wilhelmy, Julie; McSween, Alana M; Palanski, Brad A; Mallajosyula, Venkata Vamsee Aditya; Bracey, Nathan A; Dhondalay, Gopal Krishna R; Bhamidipati, Kartik; Pai, Joy; Kipp, Lucas B; Dunn, Jeffrey E; Hauser, Stephen L; Oksenberg, Jorge R; Satpathy, Ansuman T; Robinson, William H; Dekker, Cornelia L; Steinmetz, Lars M; Khosla, Chaitan; Utz, Paul J; Sollid, Ludvig M; Chien, Yueh-Hsiu; Heath, James R; Fernandez-Becker, Nielsen Q; Nadeau, Kari C; Saligrama, Naresha; and Davis, Mark M, "KIR + CD8 + T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19" (2022). Articles, Abstracts, and Reports. 5901.