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; 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; Heather M. Long; Jacob D. Estes; Meinrad Busslinger; Gabrielle T. Belz; Sharon R. Lewin; Axel Kallies; Di Yu

doi:10.1038/ni.3543

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 journal › Article › peer-review

336 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 (T_FH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (T_C cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected T_FH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (T_FCcells), 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 T_FCcell development. The identification of T_FCcells has far-reaching implications for the development of strategies to control infections that target B cells and T_FH cells and to treat B cell-derived malignancies.

Original language	English (US)
Pages (from-to)	1187-1196
Number of pages	10
Journal	Nature Immunology
Volume	17
Issue number	10
DOIs	https://doi.org/10.1038/ni.3543
State	Published - Sep 20 2016
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Leong, Y. A., Chen, Y., Ong, H. S., Wu, D., Man, K., Deleage, C., Minnich, M., Meckiff, B. J., Wei, Y., Hou, Z., Zotos, D., Fenix, K. A., Atnerkar, A., Preston, S., Chipman, J. G., Beilman, G. J., Allison, C. C., Sun, L., Wang, P., ... 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

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, JD, 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

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title = "CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles",

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.",

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 McColl, {Shaun R.} and Schacker, {Timothy W.} and Long, {Heather M.} and Estes, {Jacob D.} and Meinrad Busslinger and Belz, {Gabrielle T.} and Lewin, {Sharon R.} and Axel Kallies and Di Yu",

year = "2016",

month = sep,

day = "20",

doi = "10.1038/ni.3543",

language = "English (US)",

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T1 - CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles

AU - Leong, Yew Ann

AU - Chen, Yaping

AU - Ong, Hong Sheng

AU - Wu, Di

AU - Man, Kevin

AU - Deleage, Claire

AU - Minnich, Martina

AU - Meckiff, Benjamin J.

AU - Wei, Yunbo

AU - Hou, Zhaohua

AU - Zotos, Dimitra

AU - Fenix, Kevin A.

AU - Atnerkar, Anurag

AU - Preston, Simon

AU - Chipman, Jeffrey G.

AU - Beilman, Greg J.

AU - Allison, Cody C.

AU - Sun, Lei

AU - Wang, Peng

AU - Xu, Jiawei

AU - Toe, Jesse G.

AU - Lu, Hao K.

AU - Tao, Yong

AU - Palendira, Umaimainthan

AU - Dent, Alexander L.

AU - Landay, Alan L.

AU - Pellegrini, Marc

AU - Comerford, Iain

AU - McColl, Shaun R.

AU - Schacker, Timothy W.

AU - Long, Heather M.

AU - Estes, Jacob D.

AU - Busslinger, Meinrad

AU - Belz, Gabrielle T.

AU - Lewin, Sharon R.

AU - Kallies, Axel

AU - Yu, Di

PY - 2016/9/20

Y1 - 2016/9/20

N2 - 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.

AB - 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.

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EP - 1196

JO - Nature Immunology

JF - Nature Immunology

IS - 10

ER -

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

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