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J Exp Med. 2018 Jan 2;215(1):337-355. doi: 10.1084/jem.20170457. Epub 2017 Dec 6.

STAT4 and T-bet control follicular helper T cell development in viral infections.

Author information

1
Department of Internal Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT jason.weinstein@yale.edu.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT.
3
Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
4
Department of Internal Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT.
5
Department of Pathology and Genetics, Yale University School of Medicine, New Haven, CT.
6
Department of Internal Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT joseph.craft@yale.edu.

Abstract

Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and proliferation and guide their differentiation and immunoglobulin isotype switching by delivering contact-dependent and soluble factors, including IL-21, IL-4, IL-9, and IFN-γ. IL-21 and IFN-γ are coexpressed by Tfh cells during viral infections, but transcriptional regulation of these cytokines is not completely understood. In this study, we show that the T helper type 1 cell (Th1 cell) transcriptional regulators T-bet and STAT4 are coexpressed with Bcl6 in Tfh cells after acute viral infection, with a temporal decline in T-bet in the waning response. T-bet is important for Tfh cell production of IFN-γ, but not IL-21, and for a robust GC reaction. STAT4, phosphorylated in Tfh cells upon infection, is required for expression of T-bet and Bcl6 and for IFN-γ and IL-21. These data indicate that T-bet is expressed with Bcl6 in Tfh cells and is required alongside STAT4 to coordinate Tfh cell IL-21 and IFN-γ production and for promotion of the GC response after acute viral challenge.

PMID:
29212666
PMCID:
PMC5748849
DOI:
10.1084/jem.20170457
[Indexed for MEDLINE]
Free PMC Article

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