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https://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. |
DOI: | 10.1038/ni.3543 |
Published version: | http://www.nature.com/ni/journal/v17/n10/full/ni.3543.html |
Appears in Collections: | Aurora harvest 3 Molecular and Biomedical Science publications |
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