Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
J Clin Invest. 2012 Sep;122(9):3281-94. doi: 10.1172/JCI63039. Epub 2012 Aug 27.
CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation in SIV-induced antibody production is not well understood. We investigated the phenotype, function, location, and molecular signature of TFH cells in rhesus macaques. Similar to their human counterparts, TFH cells in rhesus macaques represented a heterogeneous population with respect to cytokine function. In a highly differentiated subpopulation of TFH cells, characterized by CD150lo expression, production of Th1 cytokines was compromised while IL-4 production was augmented, and cells exhibited decreased survival, cycling, and trafficking capacity. TFH cells exhibited a distinct gene profile that was markedly altered by SIV infection. TFH cells were infected by SIV; yet, in some animals, these cells actually accumulated during chronic SIV infection. Generalized immune activation and increased IL-6 production helped drive TFH differentiation during SIV infection. Accumulation of TFH cells was associated with increased frequency of activated germinal center B cells and SIV-specific antibodies. Therefore, chronic SIV does not disturb the ability of TFH cells to help B cell maturation and production of SIV-specific immunoglobulins.
CD4+ 滤泡辅助性 T（TFH）细胞与抗原特异性 B 细胞相互作用并刺激其生成。TFH 细胞与 B 细胞的相互作用与 SIV 特异性免疫球蛋白的产生相关。然而，TFH 细胞的命运及其在 SIV 诱导的抗体产生中的作用尚不清楚。我们研究了恒河猴 TFH 细胞的表型、功能、位置和分子特征。与人类 TFH 细胞相似，恒河猴 TFH 细胞在细胞因子功能方面表现出异质性。在 TFH 细胞的一个高度分化亚群中，其特征是 CD150lo 表达，Th1 细胞因子的产生受损，而 IL-4 的产生增加，细胞的存活、循环和迁移能力降低。TFH 细胞表现出独特的基因谱，该基因谱因 SIV 感染而明显改变。TFH 细胞被 SIV 感染；然而，在一些动物中，这些细胞在慢性 SIV 感染期间实际上会积累。普遍的免疫激活和增加的 IL-6 产生有助于驱动 SIV 感染期间 TFH 分化。TFH 细胞的积累与激活的生发中心 B 细胞和 SIV 特异性抗体的频率增加有关。因此，慢性 SIV 不会干扰 TFH 细胞帮助 B 细胞成熟和产生 SIV 特异性免疫球蛋白的能力。
