The Transcription Factor T-Bet Is Required for Optimal Type I Follicular Helper T Cell Maintenance During Acute Viral Infection.

Pengcheng Wang,Lifan Xu,Jialin Wu,Yaxing Hao,Qizhao Huang,Ran He,Luoyingzi Xie,Youping Wang,Xiangyu Chen,Yaokai Chen,Qiang Bai,Yuzhang Wu,Minglu Xiao,Lilin Ye,Baohua Li,Sen Yang

doi:10.3389/fimmu.2019.00606

Abstract

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.

Highlights

Because of the complexity and diversity of pathogens, organisms have developed highly organized and well-adapted immune systems to eliminate invaders
Based on the expression of CD44 and CXCR5, FOXP3−CD4+ T cells were divided into three subsets, CD44+CXCR5+, CD44+CXCR5−, FIGURE 1 | Transcription factor T-bet is selectively expressed in Type I but not Type II TFH cells. (A–F) WT C57BL/6 mice were infected with LCMV, Listeria monocytogenes (LM), or immunized with NP-KLH
In the NP-KLH immunization model, there is nearly no detectable T-bet expression in both TFH cells and non-TFH cells (Figure 1F). These data demonstrated that T-bet is selectively expressed in TFH cells derived from type I rather than type II immune responses, suggesting that unlike common transcription factors such as TCF1 or Bcl6, T-bet may be an immune response type-dependent feature of TFH cells

Summary

Introduction

Because of the complexity and diversity of pathogens, organisms have developed highly organized and well-adapted immune systems to eliminate invaders. Type-1 TFH Maintenance Requires T-Bet responses [7, 8]; venoms or helminthes induce type II immune response, which includes IL-4-producing ILC2s [9,10,11], TH2 cells [6, 12], and TC2 cells [7, 13]; and extracellular fungi or bacteria induce type III immune response, which comprises IL17-producing ILC3s [14, 15], TH17 cells [16,17,18], and TC17 cells [19, 20] This phenomenon reflects the high plasticity and environmental dependency of immune cells. TFH cells facilitate the differentiation of memory B cells and long-lived plasma cells from GC B cells [21, 22, 46]

Methods

Results

Conclusion