Institute of Immunology, PLA, Third Military Medical University, Chongqing, China.
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, China.
Front Immunol. 2019 Mar 29;10:606. doi: 10.3389/fimmu.2019.00606. eCollection 2019.
Follicular helper T cells (TFH cells), known as the primary "helpers" of the germinal center (GC) reaction, promote the humoral immune response to defend against various pathogens. Under conditions of infection by different types of pathogens, many shared transcription factors (TFs), such as Bcl-6, TCF-1, and Maf, are selectively enriched in pathogen-specific TFH cells, orchestrating TFH cell differentiation and function. In addition, TFH cells also coexpress environmentally associated TFs as their conventional T cell counterparts (such as T-bet, GATA-3, or ROR-γt, which are expressed in Th1, Th2, or Th17 cells, respectively). These features likely indicate both the lineage-specificity and environmental adaption of the TFH cell responses. However, the extent to which the TFH cell response relies on these environmentally specific TFs is not completely understood. Here, we found that T-bet was specifically expressed in Type I TFH cells but not Type II TFH cells. While dispensable for the early fate commitment of TFH cells, T-bet was essential for the maintenance of differentiated TFH cells, promoting their proliferation, and inhibiting their apoptosis during acute viral infection. Microarray analysis showed both similarities and differences in transcriptome dependency on T-bet in TFH and TH1 cells, suggesting the distinctive role of T-bet in TFH cells. Collectively, our findings reveal an important and specific supporting role for T-bet in type I TFH cell response, which can help us gain a deeper understanding of TFH cell subsets.
滤泡辅助 T 细胞（TFH 细胞），作为生发中心（GC）反应的主要“辅助者”，促进了针对各种病原体的体液免疫反应。在感染不同类型病原体的情况下，许多共享的转录因子（TFs），如 Bcl-6、TCF-1 和 Maf，在病原体特异性 TFH 细胞中被选择性富集，协调 TFH 细胞分化和功能。此外，TFH 细胞还共同表达环境相关的 TFs，与它们的常规 T 细胞对应物（如在 Th1、Th2 或 Th17 细胞中表达的 T-bet、GATA-3 或 ROR-γt）一样。这些特征可能表明 TFH 细胞反应的谱系特异性和环境适应性。然而，TFH 细胞反应在多大程度上依赖于这些环境特异性 TFs 尚不完全清楚。在这里，我们发现 T-bet 特异性表达于 I 型 TFH 细胞而不是 II 型 TFH 细胞。虽然 T-bet 对 TFH 细胞的早期命运决定不是必需的，但它对分化的 TFH 细胞的维持是必需的，促进它们在急性病毒感染期间的增殖和抑制凋亡。微阵列分析显示 TFH 和 TH1 细胞中转录组对 T-bet 的依赖性既有相似之处也有不同之处，表明 T-bet 在 TFH 细胞中的独特作用。总的来说，我们的研究结果揭示了 T-bet 在 I 型 TFH 细胞反应中发挥着重要而特定的支持作用，这有助于我们更深入地了解 TFH 细胞亚群。
