Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany.
Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, Inserm, Toulouse, U1291, France.
Eur J Immunol. 2021 Jun;51(6):1325-1333. doi: 10.1002/eji.202049148. Epub 2021 Apr 9.
T follicular helper (Tfh) cells play an essential role in regulating the GC reaction and, consequently, the generation of high-affinity antibodies and memory B cells. Therefore, Tfh cells are critical for potent humoral immune responses against various pathogens and their dysregulation has been linked to autoimmunity and cancer. Tfh cell differentiation is a multistep process, in which cognate interactions with different APC types, costimulatory and coinhibitory pathways, as well as cytokines are involved. However, it is still not fully understood how a subset of activated CD4 T cells begins to express the Tfh cell-defining chemokine receptor CXCR5 during the early stage of the immune response, how some CXCR5 pre-Tfh cells enter the B-cell follicles and mature further into GC Tfh cells, and how Tfh cells are maintained in the memory compartment. In this review, we discuss recent advances on how antigen and cognate interactions are important for Tfh cell differentiation and long-term persistence of Tfh cell memory, and how this is relevant to the current understanding of COVID-19 pathogenesis and the development of potent SARS-CoV-2 vaccines.
滤泡辅助性 T（Tfh）细胞在调节 GC 反应中发挥着重要作用，从而产生高亲和力的抗体和记忆 B 细胞。因此，Tfh 细胞对于针对各种病原体的有效体液免疫反应至关重要，其失调与自身免疫和癌症有关。Tfh 细胞分化是一个多步骤的过程，其中涉及与不同 APC 类型的同源相互作用、共刺激和共抑制途径以及细胞因子。然而，人们仍不完全了解在免疫反应的早期阶段，一部分激活的 CD4 T 细胞如何开始表达 Tfh 细胞定义性趋化因子受体 CXCR5，以及一些 CXCR5 前 Tfh 细胞如何进入 B 细胞滤泡并进一步成熟为 GC Tfh 细胞，以及 Tfh 细胞如何在记忆区室中维持。在这篇综述中，我们讨论了抗原和同源相互作用如何对 Tfh 细胞分化和 Tfh 细胞记忆的长期维持很重要，以及这与当前对 COVID-19 发病机制和有效 SARS-CoV-2 疫苗开发的理解有何关系。
