Human follicular helper T lymphocytes critical players in antibody responses

ABSTRACT Follicular helper T lymphocytes are a subpopulation of CD4+ T lymphocytes initially identified in germinal centers of follicles found in secondary lymphoid organs. The primary function of follicular helper T lymphocytes is to help B lymphocytes’ antibody production. Changing of antibody class and affinity, B cell differentiation and memory generation depend on cooperation between follicular helper T lymphocytes and B cells. In blood, follicular helper T lymphocytes are called circulating follicular helper T lymphocytes. They are considered to have specificities similar to those developed in the secondary lymphoid organs. The phenotype of human follicular helper T lymphocytes is given by simultaneous expression of the markers CXCR5, Bcl-6, CD40L, PD-1, and ICOS. In germinal centers, follicular helper T lymphocytes synthesize interleukin 21 as predominant cytokine. In blood, subpopulations of circulating follicular helper T lymphocytes can be recognized, with different expressions of the classical follicular helper T lymphocytes markers and, in addition, can express other markers such as CXCR3 and CCR6. Presently, there is great interest in follicular helper T lymphocytes and circulating follicular helper T lymphocytes in vaccination studies as indicators of immunization efficacy. In addition, follicular helper T lymphocytes are investigated as possible markers of activity in many diseases and potential therapeutic intervention. This short review describes aspects of immunobiology and quantification of follicular helper T lymphocytes and circulating follicular helper T lymphocytes, and presents a few examples of related findings in systemic lupus erythematosus, rheumatoid arthritis, HIV infection and vaccination.

摘要：滤泡辅助性T淋巴细胞（Follicular helper T lymphocytes）是CD4+T淋巴细胞（CD4+ T lymphocytes）的一个亚群，最初在次级淋巴器官（secondary lymphoid organs）滤泡的生发中心（germinal centers）中被鉴定发现。滤泡辅助性T淋巴细胞的核心功能是辅助B淋巴细胞产生抗体。抗体类别转换、亲和力成熟、B细胞分化以及记忆细胞生成，均依赖于滤泡辅助性T淋巴细胞与B细胞的协同互作。在血液中，滤泡辅助性T淋巴细胞被称为循环滤泡辅助性T淋巴细胞（circulating follicular helper T lymphocytes），其特性被认为与次级淋巴器官中发育的滤泡辅助性T淋巴细胞相似。人类滤泡辅助性T淋巴细胞的表型，以同时表达CXCR5、Bcl-6、CD40L、PD-1及ICOS等标志物为特征。在生发中心内，滤泡辅助性T淋巴细胞以合成分泌白细胞介素21（interleukin 21）作为主要效应细胞因子（cytokine）。在血液中，可识别出循环滤泡辅助性T淋巴细胞的多个亚群，这些亚群不仅存在经典滤泡辅助性T淋巴细胞标志物的表达差异，还可表达CXCR3、CCR6等其他标志物。目前，滤泡辅助性T淋巴细胞与循环滤泡辅助性T淋巴细胞作为免疫效力评价指标，在疫苗接种研究中受到广泛关注。此外，滤泡辅助性T淋巴细胞也被研究作为多种疾病的疾病活动标志物及潜在治疗干预靶点。本简要综述阐述了滤泡辅助性T淋巴细胞与循环滤泡辅助性T淋巴细胞的免疫生物学特性及量化检测方法，并列举了其在系统性红斑狼疮（systemic lupus erythematosus）、类风湿关节炎（rheumatoid arthritis）、HIV感染及疫苗接种相关研究中的若干相关发现实例。