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|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|
|Citation:||Nature Immunology, 2016; 17(10):1187-1196|
|Publisher:||Nature Publishing Group|
|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.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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