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 Estes, Meinrad Busslinger, Gabrielle T. Belz, Sharon R. Lewin, Axel Kallies, Di Yu

Research output: Contribution to journalArticle

125 Citations (Scopus)

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
Externally publishedYes

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Virus Diseases
B-Lymphocytes
T-Lymphocytes
TCF Transcription Factors
Chemokine Receptors
Infection Control
Helper-Inducer T-Lymphocytes
Human Herpesvirus 4
Cell Differentiation
HIV
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Leong, Y. A., Chen, Y., Ong, H. S., Wu, D., Man, K., Deleage, C., ... Yu, D. (2016). CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles. Nature Immunology, 17(10), 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; McColl, Shaun R.; Schacker, Timothy W.; Long, Heather M.; Estes, Jacob; Busslinger, Meinrad; Belz, Gabrielle T.; Lewin, Sharon R.; Kallies, Axel; Yu, Di.

In: Nature Immunology, Vol. 17, No. 10, 20.09.2016, p. 1187-1196.

Research output: Contribution to journalArticle

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, McColl, SR, Schacker, TW, Long, HM, Estes, J, Busslinger, M, Belz, GT, Lewin, SR, Kallies, A & 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
Leong YA, Chen Y, Ong HS, Wu D, Man K, Deleage C et al. CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles. Nature Immunology. 2016 Sep 20;17(10):1187-1196. https://doi.org/10.1038/ni.3543
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 ; McColl, Shaun R. ; Schacker, Timothy W. ; Long, Heather M. ; Estes, Jacob ; Busslinger, Meinrad ; Belz, Gabrielle T. ; Lewin, Sharon R. ; Kallies, Axel ; 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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