KIR+CD8+ 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; 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

doi:10.1126/science.abi9591

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

Science. 2022 Apr 15;376(6590):eabi9591. doi: 10.1126/science.abi9591. Epub 2022 Apr 15.

Authors

Jing Li¹, Maxim Zaslavsky², Yapeng Su³, Jing Guo⁴, Michael J Sikora⁵, Vincent van Unen¹, Asbjørn Christophersen^{6

7

8}, Shin-Heng Chiou¹, Liang Chen¹, Jiefu Li⁹, Xuhuai Ji¹⁰, Julie Wilhelmy¹, Alana M McSween¹, Brad A Palanski¹¹, Venkata Vamsee Aditya Mallajosyula¹, Nathan A Bracey¹, Gopal Krishna R Dhondalay¹², Kartik Bhamidipati¹³, Joy Pai¹³, Lucas B Kipp¹⁴, Jeffrey E Dunn¹⁴, Stephen L Hauser¹⁵, Jorge R Oksenberg¹⁵, Ansuman T Satpathy¹⁶, William H Robinson^{17

18}, Cornelia L Dekker¹⁹, Lars M Steinmetz^{5

20

21}, Chaitan Khosla^{11

22

23}, Paul J Utz^{1

18}, Ludvig M Sollid^{6

7

8

24}, Yueh-Hsiu Chien^{1

4}, James R Heath^{3

25}, Nielsen Q Fernandez-Becker²⁶, Kari C Nadeau^{1

12}, Naresha Saligrama¹, Mark M Davis^{1

9

4}

Affiliations

¹ Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
² Program in Computer Science, Stanford University, Stanford, CA, USA.
³ Institute for Systems Biology, Seattle, WA, USA.
⁴ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
⁶ K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁸ Department of Immunology, University of Oslo, Oslo, Norway.
⁹ The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Department of Chemistry, Stanford University, Stanford, CA, USA.
¹² Sean N. Parker Center for Allergy and Asthma Research, Department of Medicine, Stanford University, Stanford, CA, USA.
¹³ Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁴ Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
¹⁵ Department of Neurology and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
¹⁶ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁷ VA Palo Alto Health Care System, Palo Alto, CA, USA.
¹⁸ Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA.
¹⁹ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
²⁰ Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA.
²¹ European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
²² Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
²³ Stanford ChEM-H, Stanford University, Stanford, CA, USA.
²⁴ Department of Immunology, Oslo University Hospital, Oslo, Norway.
²⁵ Department of Bioengineering, University of Washington, Seattle, WA, USA.
²⁶ Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoimmune Diseases*
CD8-Positive T-Lymphocytes
COVID-19*
Humans
Mice
Receptors, KIR
T-Lymphocytes, Regulatory

Substances

Receptors, KIR

Abstract

Publication types

MeSH terms

Substances

Grants and funding