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

Authors
Jing Li,Maxim Zaslavsky
Yapeng Su,Jing Guo,Michael J. Sikora,Vincent 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. Kipp,Jeffrey 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,Michael Sikora,Shin‐Heng Chiou,Alana McSween,Brad Palanski,Vamsee Mallajosyula,Nathan Bracey,Gopal Dhondalay,Lucas Kipp,Jeffrey Dunn,Stephen Hauser,Jorge Oksenberg,Ansuman Satpathy,William Robinson,Cornelia Dekker,Lars Steinmetz,Paul Utz,Ludvig Sollid,Yueh‐hsiu Chien,James Heath,Nielsen Fernandez‐Becker,Kari Nadeau
+55 authors
,Mark Davis
Journal
Published
Apr 15, 2022
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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.

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