Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus
File(s)
Published version
Author(s)
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.
Date Issued
2016-11-01
Date Acceptance
2016-10-04
Citation
Cell Reports, 2016, 17 (6), pp.1571-1583
ISSN
2211-1247
Publisher
Elsevier
Start Page
1571
End Page
1583
Journal / Book Title
Cell Reports
Volume
17
Issue
6
Copyright Statement
© 2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000386936200010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
RETROVIRAL INFECTION
VIRAL-INFECTION
LYMPHOCYTES-T
B-CELLS
IMMUNITY
DIFFERENTIATION
EXPRESSION
INDUCTION
RESPONSES
ANTIGEN
Publication Status
Published
Date Publish Online
2016-11-01