Opposing development of cytotoxic and follicular helper CD4 T cells controlled by the TCF-1-Bcl6 Nexus
- Author(s)
- Donnarumma, T; Young, GR; Merkenschlager, J; Eksmond, U; Bongard, N; Nutt, SL; Boyer, C; Dittmer, U; Le-Trilling, VT; Trilling, M; Bayer, W; Kassiotis, G;
- Details
- Publication Year 2016-11-01,Volume 17,Issue #6,Page 1571-1583
- Journal Title
- Cell Rep
- Publication Type
- Journal Article
- Abstract
- CD4+ T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8+ T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4+ T cells. However, the conditions that induce CD4+ CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)+ CD4+ CTLs, which distinguishes them from other CD4+ T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4+ CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors Bcl6 and Tcf7 (encoding TCF-1) and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4+ CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4+ T cells with either helper or killer functions.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Immunology
- PubMed ID
- 27806296
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2016.10.013
- Open Access at Publisher's Site
http://www.sciencedirect.com/science/article/pii/S2211124716313997- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-11-14 11:36:21
Last Modified: 2016-11-17 01:49:45