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Hoste, Levi; Roels, Lisa; Naesens, Leslie; Bosteels, Victor; Vanhee, Stijn; Dupont, Sam; Bosteels, Cedric; Browaeys, Robin; Vandamme, Niels; Verstaen, Kevin; Roels, Jana; Van Damme, Karel F.A.; Maes, Bastiaan; De Leeuw, Elisabeth; Declercq, Jozefien; Aegerter, Helena; Seys, Leen; Smole, Ursula; De Prijck, Sofie; Vanheerswynghels, Manon; Claes, Karlien; Debacker, Veronique; Van Isterdael, Gert; Backers, Lynn; [...]

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

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  • Media type: E-Article
  • Title: TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C
  • Contributor: Hoste, Levi; Roels, Lisa; Naesens, Leslie; Bosteels, Victor; Vanhee, Stijn; Dupont, Sam; Bosteels, Cedric; Browaeys, Robin; Vandamme, Niels; Verstaen, Kevin; Roels, Jana; Van Damme, Karel F.A.; Maes, Bastiaan; De Leeuw, Elisabeth; Declercq, Jozefien; Aegerter, Helena; Seys, Leen; Smole, Ursula; De Prijck, Sofie; Vanheerswynghels, Manon; Claes, Karlien; Debacker, Veronique; Van Isterdael, Gert; Backers, Lynn; [...]
  • imprint: Rockefeller University Press, 2022
  • Published in: Journal of Experimental Medicine
  • Language: English
  • DOI: 10.1084/jem.20211381
  • ISSN: 1540-9538; 0022-1007
  • Keywords: Immunology ; Immunology and Allergy
  • Origination:
  • Footnote:
  • Description: <jats:p>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.</jats:p>
  • Access State: Open Access