CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles
- Author(s)
- Leong, YA; Chen, Y; Ong, HS; Wu, D; Man, K; Deleage, C; Minnich, M; Meckiff, BJ; Wei, Y; Hou, Z; Zotos, D; Fenix, KA; Atnerkar, A; Preston, S; Chipman, JG; Beilman, GJ; Allison, CC; Sun, L; Wang, P; Xu, J; Toe, JG; Lu, HK; Tao, Y; Palendira, U; Dent, AL; Landay, AL; Pellegrini, M; Comerford, I; McColl, SR; Schacker, TW; Long, HM; Estes, JD; Busslinger, M; Belz, GT; Lewin, SR; Kallies, A; Yu, D;
- Journal Title
- Nature Immunology
- Publication Type
- Journal Article
- 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.
- Publisher
- NPG
- Research Division(s)
- Molecular Immunology; Infection And Immunity
- PubMed ID
- 27487330
- Publisher's Version
- https://doi.org/10.1038/ni.3543
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-08-10 04:12:55
Last Modified: 2018-07-11 09:26:35