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

Publication Title

Science

Document Type

Article

Publication Date

4-15-2022

Keywords

covid-19; washington; seattle; isb; Animals; Autoimmune Diseases; CD8-Positive T-Lymphocytes; COVID-19; Humans; Mice; Receptors, KIR; T-Lymphocytes, Regulatory

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.

Specialty

Infectious Diseases

Specialty

Institute for Systems Biology

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