Characterization of SARS-CoV-2 and common cold coronavirus-specific T-cell responses in MIS-C and Kawasaki disease children.
Characterization of SARS-CoV-2 and common cold coronavirus-specific T-cell responses in MIS-C and Kawasaki disease children.
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DOI：
10.1002/eji.202149556
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发表时间：
2022-01
影响因子：
5.4
通讯作者：
Franco A
中科院分区：
文献类型：
--
作者：
Hsieh LE;Grifoni A;Sidney J;Shimizu C;Shike H;Ramchandar N;Moreno E;Tremoulet AH;Burns JC;Franco A
儿童在接触SARS-CoV-2后发生多系统炎症综合征（MIS-C）的免疫发病机制尚未完全了解。在这里，我们研究了MIS-C，川崎（KD）和SARS-CoV-2恢复期对照中的SARS-CoV-2特异性T细胞，使用来自SARS-CoV-2刺突蛋白或非刺突蛋白和普通感冒冠状病毒（CCC）的肽池。在5名对CCC具有交叉反应性的MIS-C受试者中检测到协调的CD 4+和CD 8 + SARS-CoV-2特异性T细胞。分别在3例和1例受试者中记录了单独的CD 4+和CD 8 + T细胞应答。MIS-C中的T细胞特异性与疾病严重程度无关，与SARS-CoV-2恢复期对照相似。MIS-C和SARS-CoV-2恢复期对照中的T细胞记忆和对CCC的交叉反应性也相似。趋化因子受体CCR 6（而非CCR 9）在SARS-CoV-2特异性CD 4 + T细胞上高度表达，但在CD 8 + T细胞上不表达。10例KD受试者中仅2例显示对CCC的T细胞应答。骨髓APC计数显示，与KD相比，MIS-C受试者的细胞前体较低。总之，患有MIS-C的儿童对SARS-CoV-2的T细胞反应正常，与先前的CCC暴露没有明显的关系。低数量的致耐受性髓样DC可能会损害其抗炎反应。来自患有多系统炎症综合征（MIS-C）的儿童的T细胞对SARS-CoV-2刺突和非刺突肽megapools有反应。SARS-CoV-2特异性记忆T细胞和归巢受体在CD 4+和CD 8 + T细胞之间显示出不同的模式。MIS-C受试者循环中的髓样树突状细胞非常少，包括ILT-4+ CD 4+致耐受性树突状细胞。
The immunopathogenesis of multisystem inflammatory syndrome (MIS‐C) in children that may follow exposure to SARS‐CoV‐2 is incompletely understood. Here, we studied SARS‐CoV‐2‐specific T cells in MIS‐C, Kawasaki disease (KD), and SARS‐CoV‐2 convalescent controls using peptide pools derived from SARS‐CoV‐2 spike or nonspike proteins, and common cold coronaviruses (CCC). Coordinated CD4+ and CD8+ SARS‐CoV‐2‐specific T cells were detected in five MIS‐C subjects with cross‐reactivity to CCC. CD4+ and CD8+ T‐cell responses alone were documented in three and one subjects, respectively. T‐cell specificities in MIS‐C did not correlate with disease severity and were similar to SARS‐CoV‐2 convalescent controls. T‐cell memory and cross‐reactivity to CCC in MIS‐C and SARS‐CoV‐2 convalescent controls were also similar. The chemokine receptor CCR6, but not CCR9, was highly expressed on SARS‐CoV‐2‐specific CD4+ but not on CD8+ T cells. Only two of 10 KD subjects showed a T‐cell response to CCC. Enumeration of myeloid APCs revealed low cell precursors in MIS‐C subjects compared to KD. In summary, children with MIS‐C mount a normal T‐cell response to SARS‐CoV‐2 with no apparent relationship to antecedent CCC exposure. Low numbers of tolerogenic myeloid DCs may impair their anti‐inflammatory response. T cells derived from children with multisystem inflammatory syndrome (MIS‐C) respond to SARS‐CoV‐2 spike and nonspike peptide megapools. SARS‐CoV‐2‐specific memory T cells and homing receptors showed different patterns between CD4+ and CD8+ T cells. MIS‐C subjects had very low myeloid dendritic cells in circulation including ILT‐4+ CD4+ tolerogenic dendritic cells.
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影响因子：
32.4
作者：
Zlotnik A;Yoshie O
通讯作者：
Yoshie O
影响因子：
64.8
作者：
Sallusto, F;Lenig, D;Lanzavecchia, A
通讯作者：
Lanzavecchia, A
DOI：
10.1038/s41577-020-00460-4
发表时间：
2020-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Lipsitch M;Grad YH;Sette A;Crotty S
通讯作者：
Crotty S
影响因子：
64.5
作者：
Moderbacher, Carolyn Rydyznski;Ramirez, Sydney, I;Crotty, Shane
通讯作者：
Crotty, Shane
影响因子：
4.1
作者：
Carrasco Pro, Sebastian;Sidney, John;Sette, Alessandro
通讯作者：
Sette, Alessandro