Follicular helper CD4⁺ T (TFH) cells are a specialized subset of effector T cells that play a central role in orchestrating adaptive immunity. TFH cells mainly promote germinal center (GC) formation, provide help to B cells for immunoglobulin affinity maturation and class-switch recombination of B cells, and facilitate production of long-lived plasma cells and memory B cells. TFH cells express the nuclear transcriptional repressor B cell lymphoma 6 (Bcl-6), the chemokine (C-X-C motif) receptor 5 (CXCR5), the CD28 family members programmed cell death protein-1 (PD-1) and inducible costimulator (ICOS) and are also responsible for the secretion of interleukin-21 (IL-21) and IL-4. Follicular regulatory CD4+ T (TFR) cells, as a regulatory counterpart of TFH cells, participate in the regulation of GC reactions. TFR cells not only express markers of TFH cells but also express markers of regulatory T (Treg) cells containing FOXP3, glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte antigen 4 (CTLA-4), and IL-10, hence owing to the dual characteristic of TFH cells and Treg cells. ICOS, expressed on activated CD4⁺ effector T cells, participates in T cell activation, differentiation, and effector process. The expression of ICOS is highest on TFH and TFR cells, indicating it as a key regulator of humoral immunity. Multiple sclerosis (MS) is a severe autoimmune disease that affects the central nervous system and results in disability, mediated by autoreactive T cells with evolving evidence of a remarkable contribution from humoral responses. This review summarizes recent advances regarding TFH cells, TFR cells, and ICOS, as well as their functional characteristics in relation to MS.

中文翻译：

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滤泡辅助 CD4+ T 细胞、滤泡调节性 CD4+ T 细胞和诱导型共刺激物及其在多发性硬化和实验性自身免疫性脑脊髓炎中的作用

卵泡辅助 CD4 ⁺T (TFH) 细胞是效应 T 细胞的一个特殊子集，在协调适应性免疫中起核心作用。TFH细胞主要促进生发中心（GC）的形成，为B细胞的免疫球蛋白亲和力成熟和B细胞的类别转换重组提供帮助，并促进长寿浆细胞和记忆B细胞的产生。TFH 细胞表达核转录抑制因子 B 细胞淋巴瘤 6 (Bcl-6)、趋化因子 (CXC 基序) 受体 5 (CXCR5)、CD28 家族成员程序性细胞死亡蛋白 1 (PD-1) 和诱导型共刺激物 (ICOS)并且还负责白细胞介素 21 (IL-21) 和 IL-4 的分泌。滤泡调节性 CD4+ T (TFR) 细胞作为 TFH 细胞的调节对应物，参与 GC 反应的调节。TFR 细胞不仅表达 TFH 细胞的标志物，还表达调节性 T (Treg) 细胞的标志物，包括 FOXP3、糖皮质激素诱导的肿瘤坏死因子受体 (GITR)、细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 和 IL-10，因此，由于 TFH 细胞和 Treg 细胞的双重特性。ICOS，在活化的 CD4 上表达⁺效应 T 细胞，参与 T 细胞活化、分化和效应过程。ICOS在TFH和TFR细胞中的表达最高，表明它是体液免疫的关键调节因子。多发性硬化症 (MS) 是一种严重的自身免疫性疾病，它会影响中枢神经系统并导致残疾，由自身反应性 T 细胞介导，不断有证据表明体液反应的显着贡献。本综述总结了 TFH 细胞、TFR 细胞和 ICOS 的最新进展，以及它们与 MS 相关的功能特征。