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 Xu & 10 others Jesse G Toe, Hao K Lu, Yong Tao, Umaimainthan Palendira, Alexander L Dent, Alan L Landay, Marc Pellegrini, Iain Comerford, Sharon R Lewin, Di Yu

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1187-1196
Number of pages10
JournalNature Immunology
Volume17
Issue number10
DOIs
Publication statusPublished - 3 Aug 2016

Keywords

  • HIV infections
  • lymphocyte differentiation

Cite this

Leong, Yew Ann ; Chen, Yaping ; Ong, Hong Sheng ; Wu, Di ; Man, Kevin ; Deleage, Claire ; Minnich, Martina ; Meckiff, Benjamin J. ; Wei, Yunbo ; Hou, Zhaohua ; Zotos, Dimitra ; Fenix, Kevin A. ; Atnerkar, Anurag ; Preston, Simon ; Chipman, Jeffrey G ; Beilman, Greg J ; Allison, Cody C ; Sun, Lei ; Wang, Peng ; Xu, Jiawei ; Toe, Jesse G ; Lu, Hao K ; Tao, Yong ; Palendira, Umaimainthan ; Dent, Alexander L ; Landay, Alan L ; Pellegrini, Marc ; Comerford, Iain ; Lewin, Sharon R ; Yu, Di. / CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles. In: Nature Immunology. 2016 ; Vol. 17, No. 10. pp. 1187-1196.
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keywords = "HIV infections, lymphocyte differentiation",
author = "Leong, {Yew Ann} and Yaping Chen and Ong, {Hong Sheng} and Di Wu and Kevin Man and Claire Deleage and Martina Minnich and Meckiff, {Benjamin J.} and Yunbo Wei and Zhaohua Hou and Dimitra Zotos and Fenix, {Kevin A.} and Anurag Atnerkar and Simon Preston and Chipman, {Jeffrey G} and Beilman, {Greg J} and Allison, {Cody C} and Lei Sun and Peng Wang and Jiawei Xu and Toe, {Jesse G} and Lu, {Hao K} and Yong Tao and Umaimainthan Palendira and Dent, {Alexander L} and Landay, {Alan L} and Marc Pellegrini and Iain Comerford and Lewin, {Sharon R} and Di Yu",
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Leong, YA, Chen, Y, Ong, HS, Wu, D, Man, K, Deleage, C, Minnich, M, Meckiff, BJ, Wei, Y, Hou, Z, Zotos, D, Fenix, KA, Atnerkar, A, Preston, S, Chipman, JG, Beilman, GJ, Allison, CC, Sun, L, Wang, P, Xu, J, Toe, JG, Lu, HK, Tao, Y, Palendira, U, Dent, AL, Landay, AL, Pellegrini, M, Comerford, I, Lewin, SR & Yu, D 2016, 'CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles' Nature Immunology, vol. 17, no. 10, pp. 1187-1196. https://doi.org/10.1038/ni.3543

CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles. / Leong, Yew Ann; Chen, Yaping; Ong, Hong Sheng; Wu, Di; Man, Kevin; Deleage, Claire; Minnich, Martina; Meckiff, Benjamin J.; Wei, Yunbo; Hou, Zhaohua; Zotos, Dimitra; Fenix, Kevin A.; Atnerkar, Anurag; Preston, Simon; Chipman, Jeffrey G; Beilman, Greg J; Allison, Cody C; Sun, Lei; Wang, Peng; Xu, Jiawei; Toe, Jesse G; Lu, Hao K; Tao, Yong; Palendira, Umaimainthan; Dent, Alexander L; Landay, Alan L; Pellegrini, Marc; Comerford, Iain; Lewin, Sharon R; Yu, Di.

In: Nature Immunology, Vol. 17, No. 10, 03.08.2016, p. 1187-1196.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Meckiff, Benjamin J.

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AU - Allison, Cody C

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AU - Xu, Jiawei

AU - Toe, Jesse G

AU - Lu, Hao K

AU - Tao, Yong

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AU - Landay, Alan L

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