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Front. Immunol. | doi: 10.3389/fimmu.2019.00606

The Transcription Factor T-bet is Required for Optimal Type I Follicular Helper T Cell Maintenance during Acute Viral Infection

 Pengcheng Wang1,  Youping Wang1, Luoyingzi Xie1, Yaokai Chen2*, Yuzhang Wu1*, Lilin Ye1*,  Minglu Xiao1,  Jialin Wu1,  Lifan Xu1,  Qiang BAI1,  Yaxing Hao1,  Qizhao Huang1,  Xiangyu Chen1, Ran He1, Baohua Li1 and  Sen Yang2
  • 1Institute of Immunology, Third Military Medical University, China
  • 2Chongqing Public Health Medical Center, China

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 in mouse model of acute Lymphocytic choriomeningitis virus (LCMV) infection, T-bet was specifically expressed in virus-specific TFH cells and that the T-bet-IFN-γ axis was dispensable for the early fate commitment of TFH cells, while 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.

Keywords: T-bet, Follicular helper T cells, Type I immune response, humoral response, T cell differentiation

Received: 28 Nov 2018; Accepted: 07 Mar 2019.

Edited by:

Georgia Fousteri, San Raffaele Hospital (IRCCS), Italy

Reviewed by:

Masato Kubo, Tokyo University of Science, Japan
Colleen J. Winstead, Merck Sharp & Dohme Corp (United States), United States  

Copyright: © 2019 Wang, Wang, Xie, Chen, Wu, Ye, Xiao, Wu, Xu, BAI, Hao, Huang, Chen, He, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Yaokai Chen, Chongqing Public Health Medical Center, Chongqing, China, yaokaichen@hotmail.com
Prof. Yuzhang Wu, Institute of Immunology, Third Military Medical University, Chongqing, China, wuyuzhang@tmmu.edu.cn
Prof. Lilin Ye, Institute of Immunology, Third Military Medical University, Chongqing, China, yelilinlcmv@tmmu.edu.cn