Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14000, Mexico City, Mexico.
Autoimmun Rev. 2011 Apr;10(6):325-30. doi: 10.1016/j.autrev.2010.11.007. Epub 2010 Dec 15.
Follicular helper T cells (T(FH)) have been implicated as a lineage that provides sufficient help to B cells in order to become professional antibody producers. This T helper subset is characterized by a distinctive cell-surface phenotype (CD4(+)CD57(+)CXCR5(+)) and cytokine profile (IL-21, IL-6, and IL-27) as well as transcriptional program (BCL-6, ICOS, and PD-1). Evidence supports the concept that T(FH) subset development, as well as for other lineages, is dependent on microenvironment cues that modulate a particular transcriptional program, susceptible to plasticity. Recently, it has been shown that BCL-6 and IL-21 act as master regulators for the development and function of T(FH) cells. Moreover, costimulation via ICOS, as well as signaling proteins such as SAP constitute required elements of the regulatory network that modulates T(FH) functions. T(FH) dysregulation has been implicated in the development of autoimmune pathology, such as SLE. Indeed, the Sanroque mice associated to the mutation of Roquin, a ubiquitin ligase, essential for the regulation of ICOS and germinal center responses, constitutes a model that shares features with human SLE. Recently, the expansion of "circulating T(FH) cells" (CD4(+)CXCR5(+)ICOS(high)PD1(high)) has been described for a subset of SLE patients that share T(FH) dependent features of disease with Sanroque mice, such as glomerulonephritis and cytopenias.
滤泡辅助 T 细胞（T(FH)）被认为是为 B 细胞提供足够帮助以成为专业抗体产生细胞的谱系。这个 T 辅助亚群的特征是独特的细胞表面表型（CD4(+)CD57(+)CXCR5(+)）和细胞因子谱（IL-21、IL-6 和 IL-27）以及转录程序（BCL-6、ICOS 和 PD-1）。有证据支持这样的概念，即 T(FH)亚群的发育以及其他谱系的发育依赖于调节特定转录程序的微环境线索，容易发生可塑性。最近，已经表明 BCL-6 和 IL-21 作为 T(FH)细胞发育和功能的主调节因子。此外，ICOS 的共刺激以及 SAP 等信号蛋白构成了调节 T(FH)功能的调控网络的必需元件。T(FH)失调与自身免疫病理学的发展有关，例如系统性红斑狼疮（SLE）。事实上，与 Roquin 突变相关的 Sanroque 小鼠，Roquin 是一种泛素连接酶，对于 ICOS 和生发中心反应的调节至关重要，它构成了与人类 SLE 具有共同特征的模型。最近，描述了一部分 SLE 患者的“循环 T(FH)细胞”（CD4(+)CXCR5(+)ICOS(high)PD1(high)）的扩增，这些患者与 Sanroque 小鼠一样具有 T(FH)依赖性疾病特征，例如肾小球肾炎和血细胞减少症。
