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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.
  • Li J; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Zaslavsky M; Program in Computer Science, Stanford University, Stanford, CA, USA.
  • Su Y; Institute for Systems Biology, Seattle, WA, USA.
  • Guo J; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Sikora MJ; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • van Unen V; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Christophersen A; K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
  • Chiou SH; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Chen L; Department of Immunology, University of Oslo, Oslo, Norway.
  • Li J; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Ji X; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Wilhelmy J; The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • McSween AM; Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA, USA.
  • Palanski BA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Mallajosyula VVA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Bracey NA; Department of Chemistry, Stanford University, Stanford, CA, USA.
  • Dhondalay GKR; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Bhamidipati K; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Pai J; Sean N. Parker Center for Allergy and Asthma Research, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Kipp LB; Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Dunn JE; Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Hauser SL; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Oksenberg JR; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Satpathy AT; Department of Neurology and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
  • Robinson WH; Department of Neurology and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
  • Dekker CL; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Steinmetz LM; VA Palo Alto Health Care System, Palo Alto, CA, USA.
  • Khosla C; Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Utz PJ; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Sollid LM; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Chien YH; Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA.
  • Heath JR; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
  • Fernandez-Becker NQ; Department of Chemistry, Stanford University, Stanford, CA, USA.
  • Nadeau KC; Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
  • Saligrama N; Stanford ChEM-H, Stanford University, Stanford, CA, USA.
  • Davis MM; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
Science ; 376(6590): eabi9591, 2022 04 15.
Article in English | MEDLINE | ID: covidwho-2088383
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Autoimmune Diseases / COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abi9591

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Autoimmune Diseases / COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abi9591