TIM3+ TRBV11-2 T cells and IFNgamma signature in patrolling monocytes and CD16+ NK cells delineate MIS-C.
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 IFNgamma and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNgamma 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 TCRbeta repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNgamma as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNgamma, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.
| Authors: | 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 Ist |
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| Journal: | J Exp Med;2022Feb07; 219 (2) . doi:10.1084/jem.20211381 |
| Year: | 2022 |
| PubMed: | PMID: 34914824 (Go to PubMed) |