Journal article
CXCR5 follicular cytotoxic T cells control viral infection in B cell follicles
YA Leong, Y Chen, HS Ong, D Wu, K Man, C Deleage, M Minnich, BJ Meckiff, Y Wei, Z Hou, D Zotos, KA Fenix, A Atnerkar, S Preston, JG Chipman, GJ Beilman, CC Allison, L Sun, P Wang, J Xu Show all
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/ni.3543
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 Bli..
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Grants
Awarded by Delaney AIDS Research Enterprise
Funding Acknowledgements
We acknowledge the facilities, scientific and technical assistance of Flowcore, Monash Micro Imaging, and Monash Bioinformatics Platform (S. Archer and K. Tsyganov) at Monash University, and University of Birmingham's Human Biomaterials Resource Centre (supported through Birmingham Science City - Experimental Medicine Network of Excellence project). We thank L. Ye (Third Military Medical University) for Thy1.1 reporter constructs; C. Vinuesa (Australian National University) and S. Nutt (Walter and Eliza Hall Institute of Medical Research) for mice; R. Gloury and L. Mackiewicz for technical support; C. Dong for the list of Bcl6-bound genes; and H. Xue for the list of TCF-1-bound genes. Supported by the National Health and Medical Research Council of Australia (Y.A.L. and S.R.L.; GNT1085509 to D.Y.; and GNT1085151 to A.K.), Monash University (D.Y.), the amfAR Research Consortium on HIV Eradication (109327-59-RGRL, D.Y., S. R. L. and A. L. L.), The Creative and Novel Ideas in HIV Research Program of The International AIDS Society (D.Y.), Australian Centre for HIV and Hepatitis Virology Research (2015-69 to D.Y.), The Priority Research Program of Shandong Academy of Sciences (D.Y.), Shandong Province Taishan Scholar Program (D.Y.), the Sylvia and Charles Viertel Foundation (A.K.), the Delaney AIDS Research Enterprise to find a cure, Martin Delaney Collaboratories, the National Institute for Allergy and Infectious Diseases of the US National Institutes of Health (U19 AI096109 to S.R.L., T.W.S. and J.D.E.), Bloodwise, UK (15021 to H.M.L. and B.J.M.), the National Cancer Institute of the US National Institutes of Health (HHSN261200800001E), and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.