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

Yew Ann Leong, Yaping Chen, Hong Sheng Ong, Di Wu, Kevin Man, Claire Deleage, Martina Minnich, Benjamin J. Meckiff, 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 XuJesse 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, Heather M. Long, Jacob D. Estes, Meinrad Busslinger, Gabrielle T. Belz, Sharon R. Lewin, Axel Kallies, Di Yu

Research output: Contribution to journalArticle

158 Scopus citations

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' (TFCcells), 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 TFCcell development. The identification of TFCcells 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.

Original languageEnglish (US)
Pages (from-to)1187-1196
Number of pages10
JournalNature Immunology
Volume17
Issue number10
DOIs
StatePublished - Sep 20 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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