TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C.
J Exp Med
; 219(2)2022 02 07.
Article
in English
| MEDLINE | ID: covidwho-1984990
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 TCRß 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
Monocytes
/
T-Lymphocytes
/
Interferon-gamma
/
Receptors, IgG
/
Systemic Inflammatory Response Syndrome
/
Hepatitis A Virus Cellular Receptor 2
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Adolescent
/
Child
/
Female
/
Humans
/
Male
Language:
English
Year:
2022
Document Type:
Article
Affiliation country:
Jem.20211381
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