4.8 Article

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

Journal

SCIENCE
Volume 376, Issue 6590, Pages 265-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abi9591

Keywords

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Funding

  1. National Institute of Allergy and Infectious Diseases (NIAID) [U19-AI057229]
  2. Howard Hughes Medical Institute
  3. National Multiple Sclerosis Society (NMSS) [RG-1611-26299]
  4. Stanford Diabetes Research Center [P30DK116074]
  5. National Center for Research Resources (NCRR) [1S10OD010580-01A1]
  6. National Science Foundation Graduate Research Fellowship
  7. Wilke Family Foundation
  8. Merck
  9. Biomedical Advanced Research and Development Authority [HHSO10201600031C]
  10. NIAID [U19-AI057229, R01AI139550, U19-AI090019, R01AI125197-04]
  11. NIH/NINDS [R35NS111644]
  12. Valhalla Foundation
  13. NIH [R01DK063158]
  14. Henry Gustav Floren Trust
  15. Sunshine Foundation
  16. Sean N. Parker Center at Stanford University
  17. NMSS

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The study reveals that CD8(+) T cells expressing inhibitory receptors play a regulatory role in immune responses in both humans and mice, and their increased presence is observed in various autoimmune diseases and COVID-19 patients. The findings suggest that these regulatory CD8(+) T cells are involved in suppressing pathogenic T cells in autoimmune and infectious diseases.
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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