意大利IRCCS圣拉斐尔科学研究所Matteo Iannacone和Mirela Kuka团队的最新研究发现，I型干扰素表达的时空调节决定CD4 ⁺ T细胞的抗病毒极化。这一研究成果2020年2月17日在线发表在国际学术期刊《自然-免疫学》上。

研究人员利用具有相同T细胞表位的重组水疱性口炎病毒（VSV）或重组淋巴细胞性脉络膜脑膜炎病毒（LCMV）感染分析了CD4 ⁺ T细胞的时空动态；VSV可诱导早期有效的中和抗体，而LCMV可诱导强烈的细胞反应但不产生中和抗体。

当VSV感染时，树突状细胞在早期暴露于I型干扰素（IFN）会诱导细胞因子IL-6的产生并推动卵泡辅助性T（T_^FH）细胞的极化，而在LCMV感染时，树突状细胞在晚期暴露于I型干扰素，其不产生IL-6并分化为1型辅助性T（T_H1）细胞。因此，对I型IFN严格的时空调节会影响抗病毒CD4 ⁺ T细胞的分化，并可以此作为指导疫苗的开发和设计。

据悉，CD4 ⁺ T细胞分化为T_FH或T_H1细胞会影响体液和细胞适应性免疫之间的平衡，但尚不完全清楚病原体引起不同效应细胞的机制。

附：英文原文

Title: Spatiotemporal regulation of type I interferon expression determines the antiviral polarization of CD4 + T cells

Author: Marco De Giovanni, Valeria Cutillo, Amir Giladi, Eleonora Sala, Carmela G. Maganuco, Chiara Medaglia, Pietro Di Lucia, Elisa Bono, Claudia Cristofani, Eleonora Consolo, Leonardo Giustini, Alessandra Fiore, Sarah Eickhoff, Wolfgang Kastenmller, Ido Amit, Mirela Kuka, Matteo Iannacone

Issue&Volume: 2020-02-17

Abstract: Differentiation of CD4+ T cells into either follicular helper T (TFH) or type 1 helper T (TH1) cells influences the balance between humoral and cellular adaptive immunity, but the mechanisms whereby pathogens elicit distinct effector cells are incompletely understood. Here we analyzed the spatiotemporal dynamics of CD4+ T cells during infection with recombinant vesicular stomatitis virus (VSV), which induces early, potent neutralizing antibodies, or recombinant lymphocytic choriomeningitis virus (LCMV), which induces a vigorous cellular response but inefficient neutralizing antibodies, expressing the same T cell epitope. Early exposure of dendritic cells to type I interferon (IFN), which occurred during infection with VSV, induced production of the cytokine IL-6 and drove TFH cell polarization, whereas late exposure to type I IFN, which occurred during infection with LCMV, did not induce IL-6 and allowed differentiation into TH1 cells. Thus, tight spatiotemporal regulation of type I IFN shapes antiviral CD4+ T cell differentiation and might instruct vaccine design strategies.

DOI: 10.1038/s41590-020-0596-6

Source: https://www.nature.com/articles/s41590-020-0596-6