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

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…

• NS
  National Science Foundation
• HH
  Howard Hughes Medical Institute
• NM
  National Multiple Sclerosis Society

  Award: RG-1611-26299
• BS
  Bristol-Myers Squibb
• GS
  Gilead Sciences

  Award: COVID-19
• B
  Biogen
• AP
  Alexion Pharmaceuticals
• C
  Celgene
• FH
  F. Hoffmann-La Roche
• SD
  Stanford Diabetes Research Center

  Award: P30DK116074
• VF
  Valhalla Foundation
• MS
  Multiple Sclerosis Society
• UI
  Universitetet i Oslo
• NI
  National Institutes of Health

  Awards: U19-AI057229, AI057229, R01AI125197, COVID-19, 1S10OD010580, U19-AI090019, P30DK116074, R01DK063158, R35NS111644, S10OD018220, AI090019
• G
  Genentech
• BA
  Biomedical Advanced Research and Development Authority

  Award: HHSO10201600031C
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: R01AI139550, COVID-19, AI090019, U19-AI090019, R01AI125197, AI057229, U19-AI057229
• NI
  National Institute of Neurological Disorders and Stroke

  Award: R35NS111644
• NC
  National Center for Research Resources

  Awards: 1S10OD010580-01A1, 1S10OD010580
• JP
  Janssen Pharmaceuticals