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Elife. 2015 Jan 8;4:e04851. doi: 10.7554/eLife.04851.

The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa.

Author information

1
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
2
Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.

Abstract

T follicular helper cells (Tfh) are crucial for the initiation and maintenance of germinal center (GC) reactions and high affinity, isotype-switched antibody responses. In this study, we demonstrate that direct TGF-β signaling to CD4 T cells is important for the formation of influenza-specific Tfh cells, GC reactions, and development of isotype-switched, flu-specific antibody responses. Early during infection, TGF-β signaling suppressed the expression of the high affinity IL-2 receptor α chain (CD25) on virus-specific CD4 T cells, which tempered IL-2 signaling and STAT5 and mammalian target of rapamycin (mTOR) activation in Tfh precursor CD4 T cells. Inhibition of mTOR allowed for the differentiation of Tfh cells in the absence of TGF-βR signaling, suggesting that TGF-β insulates Tfh progenitor cells from IL-2-delivered mTOR signals, thereby promoting Tfh differentiation during acute viral infection. These findings identify a new pathway critical for the generation of Tfh cells and humoral responses during respiratory viral infections.

KEYWORDS:

T follicular helper cells; TGF-beta; antibody; cytokines; immunology; mouse; viral infection

PMID:
25569154
PMCID:
PMC4337607
DOI:
10.7554/eLife.04851
[Indexed for MEDLINE]
Free PMC Article

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