Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease 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 to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, 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 Vβ21.3 T cell receptor β chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients 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. Vβ21.3+ T cells from MIS-C patients 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 Vβ21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

儿童多发性炎症综合征 (MIS-C) 是 SARS-CoV-2 感染的一种迟发性严重并发症，会侵袭原本健康的儿童。由于 MIS-C 结合了川崎病和中毒性休克综合症 (TSS) 的临床特征，我们旨在比较具有这些不同病症的儿科患者的免疫学特征。我们分析了 36 例 MIS-C 病例的血液细胞因子表达、T 细胞库和表型，并与 16 例 KD、58 例 TSS 和 42 例 COVID-19 病例进行比较。我们观察到 MIS-C、TSS 和 KD 中血清炎症细胞因子（IL-6、IL-10、IL-18、TNF-α、IFNγ、CD25s、MCP1、IL-1RA）增加，而 HLA 表达较低-单核细胞中的DR。我们在 75% 的 MIS-C 患者中检测到表达 Vβ21.3 T 细胞受体 β 链可变区的活化 T 细胞在 CD4 和 CD8 亚群中出现特异性扩增，但在任何 TSS、KD 或急性 COVID-19 患者中均未检测到这种情况。 ; 这与检测到的细胞因子风暴相关。MIS-C 解决后几周内，T 细胞库恢复到基线。MIS-C 患者的 Vβ21.3+ T 细胞表达高水平的 HLA-DR、CD38 和 CX3CR1，但在体外对 SARS-CoV-2 肽的反应较弱。一致地，T 细胞扩增与特定的经典 HLA 等位基因无关。因此，我们的数据表明，MIS-C 的特点是多克隆 Vβ21.3 T 细胞扩增，并非针对 SARS-CoV-2 抗原肽，这在 KD、TSS 和急性 COVID-19 中未见。