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

Autor: Timothy W. Schacker, Axel Kallies, Heather M. Long, Zhaohua Hou, Yong Tao, Claire Deleage, Martina Minnich, Iain Comerford, Meinrad Busslinger, Yew Ann Leong, Benjamin J Meckiff, Greg J. Beilman, Lei Sun, Simon Preston, Yunbo Wei, Anurag Atnerkar, Yaping Chen, Marc Pellegrini, Kevin A. Fenix, Hong Sheng Ong, Jacob D. Estes, Shaun R. McColl, Di Wu, Hao K. Lu, Cody C. Allison, Umaimainthan Palendira, Di Yu, Peng Wang, Alan L. Landay, Jiawei Xu, Dimitra Zotos, Jesse G. Toe, Sharon R Lewin, Jeffrey G. Chipman, Gabrielle T. Belz, Alexander L. Dent, Kevin Man
Rok vydání: 2016
Předmět:
Male
Receptors
CXCR5
0301 basic medicine
Epstein-Barr Virus Infections
Immunology
Antigen presentation
Mice
Transgenic
Biology
Mice
03 medical and health sciences
Interleukin 21
0302 clinical medicine
hemic and lymphatic diseases
Basic Helix-Loop-Helix Transcription Factors
medicine
Animals
Arenaviridae Infections
Humans
Lymphocytic choriomeningitis virus
Immunology and Allergy
Cytotoxic T cell
Hepatocyte Nuclear Factor 1-alpha
Antigen-presenting cell
Cells
Cultured
B cell
B-Lymphocytes
CD40
Follicular dendritic cells
HIV
Cell Differentiation
Germinal Center
Virology
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Proto-Oncogene Proteins c-bcl-6
Interleukin 12
Cancer research
biology.protein
Positive Regulatory Domain I-Binding Factor 1
T-Lymphocytes
Cytotoxic
Transcription Factors
030215 immunology
Zdroj: Nature Immunology. 17:1187-1196
ISSN: 1529-2916
1529-2908
Popis: 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.
Databáze: OpenAIRE
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