Why multisystem inflammatory syndrome in children (MIS-C) develops after SARS-CoV-2 infection in a subset of children is unknown. We hypothesized that aberrant virus–specific T cell responses contribute to MIS-C pathogenesis. We quantified SARS-CoV-2–reactive T cells, serologic responses against major viral proteins, and cytokine responses from plasma and peripheral blood mononuclear cells in children with convalescent COVID-19, in children with acute MIS-C, and in healthy controls. Children with MIS-C had significantly lower virus-specific CD4 + and CD8 + T cell responses to major SARS-CoV-2 antigens compared with children convalescing from COVID-19. Furthermore, T cell responses in participants with MIS-C were similar to or lower than those in healthy controls. Serologic responses against spike receptor binding domain (RBD), full-length spike, and nucleocapsid were similar among convalescent COVID-19 and MIS-C, suggesting functional B cell responses. Cytokine profiling demonstrated predominant Th1 polarization of CD4 + T cells from children with convalescent COVID-19 and MIS-C, although cytokine production was reduced in MIS-C. Our findings support a role for constrained induction of anti–SARS-CoV-2–specific T cells in the pathogenesis of MIS-C.
【저자키워드】 COVID-19, Adaptive immunity, Cellular immune response, peptides, 【초록키워드】 Pathogenesis, T cells, SARS-COV-2 infection, children, Th1, cytokine, Viral proteins, CD4, CD8, MIS-C, Receptor binding domain, Peripheral blood, T cell, Viral, nucleocapsid, RBD, serologic, T cell responses, Peripheral blood mononuclear cells, plasma, SARS-CoV-2 antigen, convalescent, T cell response, cytokine production, Serologic response, Inflammatory, cytokine response, mononuclear cells, mononuclear cell, Support, Spike receptor binding domain, B cell responses, syndrome, participant, healthy controls, full-length, significantly lower, serologic responses, develop, functional, contribute, demonstrated, predominant, subset, responses against, was reduced, quantified, 【제목키워드】 children, T cell response, Inflammatory, syndrome, Limited, with COVID-19,