KIR <sup>+</sup> CD8 <sup>+</sup> T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19
-
- Jing Li
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Maxim Zaslavsky
- Program in Computer Science, Stanford University, Stanford, CA, USA.
-
- Yapeng Su
- Institute for Systems Biology, Seattle, WA, USA.
-
- Jing Guo
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
-
- Michael J. Sikora
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
-
- Vincent van Unen
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Asbjørn Christophersen
- K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
-
- Shin-Heng Chiou
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Liang Chen
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Jiefu Li
- The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
-
- Xuhuai Ji
- Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA, USA.
-
- Julie Wilhelmy
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Alana M. McSween
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Brad A. Palanski
- Department of Chemistry, Stanford University, Stanford, CA, USA.
-
- Venkata Vamsee Aditya Mallajosyula
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Nathan A. Bracey
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Gopal Krishna R. Dhondalay
- Sean N. Parker Center for Allergy and Asthma Research, Department of Medicine, Stanford University, Stanford, CA, USA.
-
- Kartik Bhamidipati
- Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
-
- Joy Pai
- Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
-
- Lucas B. Kipp
- Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
-
- Jeffrey E. Dunn
- Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
-
- Stephen L. Hauser
- Department of Neurology and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
-
- Jorge R. Oksenberg
- Department of Neurology and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
-
- Ansuman T. Satpathy
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
-
- William H. Robinson
- VA Palo Alto Health Care System, Palo Alto, CA, USA.
-
- Cornelia L. Dekker
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
-
- Lars M. Steinmetz
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
-
- Chaitan Khosla
- Department of Chemistry, Stanford University, Stanford, CA, USA.
-
- Paul J. Utz
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Ludvig M. Sollid
- K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
-
- Yueh-Hsiu Chien
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- James R. Heath
- Institute for Systems Biology, Seattle, WA, USA.
-
- Nielsen Q. Fernandez-Becker
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA.
-
- Kari C. Nadeau
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Naresha Saligrama
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
-
- Mark M. Davis
- Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
Description
<jats:p> In this work, we find that CD8 <jats:sup>+</jats:sup> T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49 <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> 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 <jats:sup>+</jats:sup> T cells efficiently eliminated pathogenic gliadin-specific CD4 <jats:sup>+</jats:sup> T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells, but not CD4 <jats:sup>+</jats:sup> regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49 <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8 <jats:sup>+</jats:sup> T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases. </jats:p>
Journal
-
- Science
-
Science 376 (6590), eabi9591-, 2022-04-15
American Association for the Advancement of Science (AAAS)
- Tweet
Details 詳細情報について
-
- CRID
- 1360298760956158208
-
- ISSN
- 10959203
- 00368075
-
- Data Source
-
- Crossref