Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102566
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Type: Journal article
Title: CXCR5⁺ follicular cytotoxic T cells control viral infection in B cell follicles
Other Titles: CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles
Author: Leong, Y.
Chen, Y.
Ong, H.
Wu, D.
Man, K.
Deleage, C.
Minnich, M.
Meckiff, B.
Wei, Y.
Hou, Z.
Zotos, D.
Fenix, K.
Atnerkar, A.
Preston, S.
Chipman, J.
Beilman, G.
Allison, C.
Sun, L.
Wang, P.
Xu, J.
et al.
Citation: Nature Immunology, 2016; 17(10):1187-1196
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 1529-2908
1529-2916
Statement of
Responsibility: 
Yew Ann Leong, Iain Comerford, Kevin A Fenix, Shaun R McColl
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.
Keywords: Germinal Center; B-Lymphocytes; T-Lymphocytes, Cytotoxic; Cells, Cultured; Animals; Mice, Inbred C57BL; Mice, Transgenic; Humans; Mice; Lymphocytic choriomeningitis virus; HIV; Epstein-Barr Virus Infections; Arenaviridae Infections; Transcription Factors; Cell Differentiation; Gene Expression Regulation; Male; Hepatocyte Nuclear Factor 1-alpha; Proto-Oncogene Proteins c-bcl-6; Basic Helix-Loop-Helix Transcription Factors; Receptors, CXCR5; Positive Regulatory Domain I-Binding Factor 1
Rights: © 2016 Nature America, Inc. All rights reserved.
RMID: 0030051762
DOI: 10.1038/ni.3543
Published version: http://www.nature.com/ni/journal/v17/n10/full/ni.3543.html
Appears in Collections:Molecular and Biomedical Science publications

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