莱布尼茨研究所Mir-Farzin Mashreghi小组报道了TGFβ将EBV与儿童多系统炎症综合征联系起来。2025年3月12日出版的《自然》发表了这项成果。

在这里，该课题组研究人员发现急性MIS-C的特征是病毒反应记忆T细胞的再激活受损，这取决于血清细胞因子TGFβ水平的升高，类似于严重COVID-19期间发生的情况。这种T细胞反应性的功能损伤伴随着T细胞、B细胞和单核细胞中tgf - β反应特征的存在以及单核细胞抗原呈递能力的降低，并且可以通过阻断tgf - β来逆转。

此外，MIS-C患者的T细胞受体库表现出表达TCRVβ21.3的T细胞扩增，类似于EBV反应性T细胞克隆，能够消除EBV感染的B细胞。此外，MIS-C患者的血清tgf - β可触发EBV再激活，这在tgf - β阻断下是可逆的。在临床上，tgf β诱导的T细胞反应性缺陷与MIS-C患者比年龄匹配的对照组有更高的EBV血清阳性率相关，同时也与EBV再激活的发生相关。他们的发现在儿童中建立了SARS-CoV-2感染与COVID-19后遗症之间的联系，其中TGFβ过量产生引发的T细胞毒性受损导致EBV再激活和随后的过度炎症。

研究人员表示，在一小部分儿童和青少年中，SARS-CoV-2感染在感染后6至8周内诱发严重急性高炎性休克，称为儿童多系统炎症综合征（MIS-C）。MIS-C的特征是特异性T细胞扩张和全身性高炎症。MIS-C的发病机制在很大程度上仍不清楚。

附：英文原文

Title: TGFβ links EBV to multisystem inflammatory syndrome in children

Author: Goetzke, Carl Christoph, Massoud, Mona, Frischbutter, Stefan, Guerra, Gabriela Maria, Ferreira-Gomes, Marta, Heinrich, Frederik, von Stuckrad, Anne Sae Lim, Wisniewski, Sebastian, Licha, Jan Robin, Bondareva, Marina, Ehlers, Lisa, Khaldi-Plassart, Samira, Javouhey, Etienne, Pons, Sylvie, Trouillet-Assant, Sophie, Ozsurekci, Yasemin, Zhang, Yu, Poli, Maria Cecilia, Discepolo, Valentina, Lo Vecchio, Andrea, Sahin, Beng, Verboom, Murielle, Hallensleben, Michael, Heuhsen, Anja Isabelle, Astudillo, Camila, Espinosa, Yazmin, Vial Cox, Maria Cecilia, Dobbs, Kerry, Delmonte, Ottavia M., Montealegre Sanchez, Gina A., Magliocco, Mary, Barron, Karyl, Danielson, Jeffrey, Petrov, Lev, Unterwalder, Nadine, Sawitzki, Birgit, Matz, Mareen, Lehmann, Katrin, Gratopp, Alexander, von Bernuth, Horst, Burkhardt, Lisa-Marie, Wiese, Niklas, Peter, Lena, Schmueck-Henneresse, Michael, Amini, Leila, Maurer, Marcus, Roehmel, Jobst Fridolin, Gewurz, Benjamin E., Yonker, Lael M., Witkowski, Mario, Kruglov, Andrey, Mall, Marcus Alexander, Su, Helen C., Ozen, Seza, Radbruch, Andreas, Belot, Alexandre, Durek, Pawel, Kallinich, Tilmann, Mashreghi, Mir-Farzin

Issue&Volume: 2025-03-12

Abstract: In a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock1 termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion2 and systemic hyperinflammation3. The pathogenesis of MIS-C remains largely unknown. Here we show that acute MIS-C is characterized by impaired reactivation of virus-reactive memory T cells, which depends on increased serum levels of the cytokine TGFβ resembling those that occur during severe COVID-19 (refs. 4,5). This functional impairment in T cell reactivity is accompanied by the presence of TGFβ-response signatures in T cells, B cells and monocytes along with reduced antigen-presentation capabilities of monocytes, and can be reversed by blocking TGFβ. Furthermore, T cell receptor repertoires of patients with MIS-C exhibit expansion of T cells expressing TCRVβ21.3, resembling Epstein–Barr virus (EBV)-reactive T cell clones capable of eliminating EBV-infected B cells. Additionally, serum TGFβ in patients with MIS-C can trigger EBV reactivation, which is reversible with TGFβ blockade. Clinically, the TGFβ-induced defect in T cell reactivity correlates with a higher EBV seroprevalence in patients with MIS-C compared with age-matched controls, along with the occurrence of EBV reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, in which impaired T cell cytotoxicity triggered by TGFβ overproduction leads to EBV reactivation and subsequent hyperinflammation.

DOI: 10.1038/s41586-025-08697-6

Source: https://www.nature.com/articles/s41586-025-08697-6