학술논문
CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles
Document Type
Report
Author
Leong, Yew Ann; Chen, Yaping; Ong, Hong Sheng; Wu, Di; Man, Kevin; Deleage, Claire; Minnich, Martina; Meckiff, Benjamin J; Wei, Yunbo; Hou, Zhaohua; Zotos, Dimitra; Fenix, Kevin A; Atnerkar, Anurag; Preston, Simon; Chipman, Jeffrey G; Beilman, Greg J; Allison, Cody C; Sun, Lei; Wang, Peng; Xu, Jiawei; Toe, Jesse G; Lu, Hao K; Tao, Yong; Palendira, Umaimainthan; Dent, Alexander L; Landay, Alan L; Pellegrini, Marc; Comerford, Iain; McColl, Shaun R; Schacker, Timothy W; Long, Heather M; Estes, Jacob D; Busslinger, Meinrad; Belz, Gabrielle T; Lewin, Sharon R; Kallies, Axel; Yu, Di
Source
Nature Immunology. October 2016, Vol. 17 Issue 10, p1187, 10 p.
Subject
Language
English
ISSN
1529-2908
Abstract
Author(s): Yew Ann Leong [1]; Yaping Chen [1]; Hong Sheng Ong [1]; Di Wu [2]; Kevin Man [3, 4]; Claire Deleage [5]; Martina Minnich [6]; Benjamin J Meckiff [7]; Yunbo [...]
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 (T[sub.FH] cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (T[sub.C] cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected T[sub.FH] cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (T[sub.FC] 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 T[sub.FC] cell development. The identification of T[sub.FC] cells has far-reaching implications for the development of strategies to control infections that target B cells and T[sub.FH] cells and to treat B cell-derived malignancies.
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 (T[sub.FH] cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (T[sub.C] cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected T[sub.FH] cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (T[sub.FC] 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 T[sub.FC] cell development. The identification of T[sub.FC] cells has far-reaching implications for the development of strategies to control infections that target B cells and T[sub.FH] cells and to treat B cell-derived malignancies.