Display options
Cite
Hoste L, Roels L, Naesens L, et al. TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C. J Exp Med. 2021;219(2)doi: 10.1084/jem.20211381.
Hoste, L., Roels, L., Naesens, L., Bosteels, V., Vanhee, S., Dupont, S., Bosteels, C., Browaeys, R., Vandamme, N., Verstaen, K., Roels, J., Van Damme, K. F. A., Maes, B., De Leeuw, E., Declercq, J., Aegerter, H., Seys, L., Smole, U., De Prijck, S., Vanheerswynghels, M., Claes, K., Debacker, V., Van Isterdael, G., Backers, L., Claes, K. B. M., Bastard, P., Jouanguy, E., Zhang, S. Y., Mets, G., Dehoorne, J., Vandekerckhove, K., Schelstraete, P., Willems, J., Stordeur, P., Janssens, S., Beyaert, R., Saeys, Y., Casanova, J. L., Lambrecht, B. N., Haerynck, F., & Tavernier, S. J. (2022). TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C. The Journal of experimental medicine, 219(2), . https://doi.org/10.1084/jem.20211381
Hoste, Levi, et al. "TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C." The Journal of experimental medicine vol. 219,2 (2022). doi: https://doi.org/10.1084/jem.20211381
Hoste L, Roels L, Naesens L, Bosteels V, Vanhee S, Dupont S, Bosteels C, Browaeys R, Vandamme N, Verstaen K, Roels J, Van Damme KFA, Maes B, De Leeuw E, Declercq J, Aegerter H, Seys L, Smole U, De Prijck S, Vanheerswynghels M, Claes K, Debacker V, Van Isterdael G, Backers L, Claes KBM, Bastard P, Jouanguy E, Zhang SY, Mets G, Dehoorne J, Vandekerckhove K, Schelstraete P, Willems J, Stordeur P, Janssens S, Beyaert R, Saeys Y, Casanova JL, Lambrecht BN, Haerynck F, Tavernier SJ. TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C. J Exp Med. 2022 Feb 07;219(2). doi: 10.1084/jem.20211381. Epub 2021 Dec 16. PMID: 34914824.
Copy Download .nbib Format: NLM
Share it on

J Exp Med. 2022 Feb 07;219(2). doi: 10.1084/jem.20211381. Epub 2021 Dec 16.

TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C.

The Journal of experimental medicine

Levi Hoste, Lisa Roels, Leslie Naesens, Victor Bosteels, Stijn Vanhee, Sam Dupont, Cedric Bosteels, Robin Browaeys, Niels Vandamme, Kevin Verstaen, Jana Roels, Karel F A Van Damme, Bastiaan Maes, Elisabeth De Leeuw, Jozefien Declercq, Helena Aegerter, Leen Seys, Ursula Smole, Sofie De Prijck, Manon Vanheerswynghels, Karlien Claes, Veronique Debacker, Gert Van Isterdael, Lynn Backers, Kathleen B M Claes, Paul Bastard, Emmanuelle Jouanguy, Shen-Ying Zhang, Gilles Mets, Joke Dehoorne, Kristof Vandekerckhove, Petra Schelstraete, Jef Willems, Patrick Stordeur, Sophie Janssens, Rudi Beyaert, Yvan Saeys, Jean-Laurent Casanova, Bart N Lambrecht, Filomeen Haerynck, Simon J Tavernier

Affiliations

  1. Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University, Ghent, Belgium.
  2. Department of Internal Medicine and Pediatrics, Division of Pediatric Pulmonology, Infectious Diseases and Inborn Errors of Immunity, Ghent University Hospital, Ghent, Belgium.
  3. Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  4. Center for Inflammation Research, Laboratory for Endoplasmic Reticulum Stress and Inflammation, VIB, Ghent, Belgium.
  5. Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  6. Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
  7. Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
  8. VIB Flow Core, VIB Center for Inflammation Research, Ghent, Belgium.
  9. Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium.
  10. Cancer Research Institute Ghent, Ghent University, Ghent, Belgium.
  11. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  12. University of Paris, Imagine Institute, Paris, France.
  13. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  14. Department of Internal Medicine and Pediatrics, Division of Pediatric Cardiology, Ghent University Hospital, Ghent, Belgium.
  15. Department of Internal Medicine and Pediatrics, Division of Pediatric Rheumatology, Ghent University Hospital, Ghent, Belgium.
  16. Department of Critical Care, Division of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.
  17. Belgian National Reference Center for the Complement System, Laboratory of Immunology, LHUB-ULB, Université Libre de Bruxelles, Brussels, Belgium.
  18. Center for Inflammation Research, Laboratory of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium.
  19. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  20. Howard Hughes Medical Institute, New York, NY.
  21. Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France.
  22. Department of Pulmonary Medicine, ErasmusMC, Rotterdam, The Netherlands.

PMID: 34914824 DOI: 10.1084/jem.20211381

Abstract

In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.

© 2021 Hoste et al.

Conflict of interest statement

Disclosures: No disclosures were reported.

Publication Types

Grant support