CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles

Research output: Contribution to journalArticlepeer-review

Authors

  • Yew Ann Leong
  • Yaping Chen
  • Hong Sheng Ong
  • Di Wu
  • Kevin Man
  • Claire Deleage
  • Martina Minnich
  • Yunbo Wei
  • Zhaohua Hou
  • Dimitra Zotos
  • Kevin A Fenix
  • Anurag Atnerkar
  • Simon Preston
  • Jeffrey G Chipman
  • Greg J Beilman
  • Cody C Allison
  • Lei Sun
  • Peng Wang
  • Jiawei Xu
  • Jesse G Toe
  • Hao K Lu
  • Yong Tao
  • Umaimainthan Palendira
  • Alexander L Dent
  • Alan L Landay
  • Marc Pellegrini
  • Iain Comerford
  • Shaun R McColl
  • Timothy W Schacker
  • Jacob D Estes
  • Meinrad Busslinger
  • Gabrielle T Belz
  • Sharon R Lewin
  • Axel Kallies
  • Di Yu

External organisations

  • Monash University

Abstract

During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC cell development. The identification of TFC cells has far-reaching implications for the development of strategies to control infections that target B cells and TFH cells and to treat B cell-derived malignancies.

Details

Original languageEnglish
Pages (from-to)1187-1196
Number of pages10
JournalNature Immunology
Volume17
Issue number10
Early online date3 Aug 2016
Publication statusPublished - Oct 2016

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