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KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19
- 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;
- Davis, Mark M
- et al.
Published Web Location
https://doi.org/10.1126/science.abi9591Abstract
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.
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