Polyclonal expansion of TCR Vβ 21.3+ CD4+ and CD8+ T cells is a hallmark of multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a delayed and severe complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease (KD) and toxic shock syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared with 16 KD, 58 TSS, and 42 coronavirus disease 2019 (COVID-19) cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-alpha, IFN-gamma, sCD25, MCP1, and IL-1RA) in MIS-C, TSS, and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the V.21.3 T cell receptor beta chain variable region in both CD4 and CD8 subsets in 75% of patients with MIS-C and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. V beta 21.3+ T cells from patients with MIS-C expressed high levels of HLA-DR, CD38, and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal V.21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS, and acute COVID-19.

Automated summary

MIS-C is characterized by increased serum inflammatory cytokines and a specific expansion of activated T cells expressing the V.21.3 T cell receptor beta chain variable region, not directed against SARS-CoV-2 antigenic peptides, which differentiates it from KD, TSS, and acute COVID-19. The T cell repertoire returns to baseline soon after MIS-C resolution.