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Cell Rep. 2016 Nov 1;17(6):1571-1583. doi: 10.1016/j.celrep.2016.10.013.

Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus.

Author information

1
Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
2
Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Retrovirus-Host Interactions, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
3
Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
4
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
5
Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, Marseille 13288, France.
6
Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, UK. Electronic address: george.kassiotis@crick.ac.uk.

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.

KEYWORDS:

CD4 T cell differentiation; adenovirus-based vaccination; antiviral immunity; cytotoxic CD4 T cells; inhibitory receptors; retroviral infection; single-cell RNA sequencing

PMID:
27806296
PMCID:
PMC5149578
DOI:
10.1016/j.celrep.2016.10.013
[Indexed for MEDLINE]
Free PMC Article

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