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Cited by 249T-cell and B-cell ImmunologyImmune Cell Function and InteractionReproductive System and Pregnancy

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

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Li, Jing, Zaslavsky, Maxim, Su, Yapeng, Guo, Jing, Sikora, Michael J., van Unen, Vincent, Christophersen, Asbjørn, Chiou, Shin-Heng +28 more·2022·Science
DOI 10.1126/science.abi9591PMC PMC8995031
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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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Authors
Li, J., Zaslavsky, M., Su, Y., Guo, J., Sikora, M. J., van Unen, V., Christophersen, A., Chiou, S.-H., Chen, L., Li, J., Ji, X., Wilhelmy, J., McSween, A. M., Palanski, B. A., Mallajosyula, V. V. A., Bracey, N. A., Dhondalay, G. K. R., Bhamidipati, K., Pai, J., Kipp, L. B., Dunn, J. E., Hauser, S. L., Oksenberg, J. R., Satpathy, A. T., Robinson, W. H., Dekker, C. L., Steinmetz, L. M., Khosla, C., Utz, P. J., Sollid, L. M., Chien, Y.-H., Heath, J. R., Fernandez-Becker, N. Q., Nadeau, K. C., Saligrama, N., & Davis, M. M.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Stanford University (US)
  • Institute for Systems Biology (US)
  • Stanford Medicine (US)
  • Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • University of Oslo (NO)
  • The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • University of California, San Francisco (US)
  • VA Palo Alto Health Care System (US)
  • Oslo University Hospital (NO)
  • University of Washington (US)
  • Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA.
Corresponding author
  • Saligrama, Naresha
  • Davis, Mark M.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-04-15
Volume
376
Issue
6590
Pages
eabi9591-eabi9591
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.abi9591
PMC
PMC8995031
OpenAlex
W4221013526
Cited by
249
References
8
Citations by year
2026: 31 · 2025: 57 · 2024: 65 · 2023: 66 · 2022: 30
FWCI
20.77
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Leiden Repository (Leiden University) (submittedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
  • National Science Foundation (S10OD018220, AI057229)
  • Howard Hughes Medical Institute
  • National Multiple Sclerosis Society (RG 1611-26299)
  • Bristol-Myers Squibb
  • Gilead Sciences (COVID-19)
  • Biogen
  • Alexion Pharmaceuticals
  • Celgene
  • F. Hoffmann-La Roche
  • Stanford Diabetes Research Center (P30DK116074)
  • Valhalla Foundation
  • Multiple Sclerosis Society
  • Agence Nationale de la Recherche (ANR-21-COVR-0033)
  • Universitetet i Oslo
  • National Institutes of Health (COVID-19, 1s10od018220-01, 1s10od010580-01a1, AI057229, AI090019)
  • Genentech
  • Biomedical Advanced Research and Development Authority (HHSO10201600031C)
  • National Institute of Allergy and Infectious Diseases (COVID-19, AI090019, AI 057229, U19AI090019, R01AI139550, R01AI125197, U19AI057229, P01AI153559, T32AI007290)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK116074, R01DK063158)
  • National Institute of Neurological Disorders and Stroke (R35NS111644)
  • National Center for Research Resources (1S10OD010580-01A1, 1S10OD010580)
  • Janssen Pharmaceuticals
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
Ly49, regulatory T cells, autoimmune disease, COVID-19 pandemic, celiac disease, T cell suppression, vasculitis, disease severity
MeSH terms
COVID-19, Animals, Autoimmune Diseases, Humans, CD8-Positive T-Lymphocytes, T-Lymphocytes, Regulatory, Mice, Receptors, KIR

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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