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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.

Heather D Marshall | John P Ray | Brian J Laidlaw | Nianzhi Zhang | Dipika Gawande | Matthew M Staron | Joe Craft | Susan M Kaech
eLife | 2015

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.

Pubmed ID: 25569154

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI074699
  • Agency: NIAMS NIH HHS, United States
    Id: R37 AR040072
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI007019
  • Agency: NIAID NIH HHS, United States
    Id: R01-AI074699
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR040072
  • Agency: NIAID NIH HHS, United States
    Id: T32-AI007019-35
  • Agency: NIAMS NIH HHS, United States
    Id: P30 AR053495
  • Agency: NIAMS NIH HHS, United States
    Id: AR053495-08
  • Agency: NIAID NIH HHS, United States
    Id: F32-AI094791
  • Agency: NIAMS NIH HHS, United States
    Id: AR40072-24
  • Agency: NIAID NIH HHS, United States
    Id: F32 AI094791

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Imaris (tool)

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B6.Cg-Tg(Lck-icre)3779Nik/J (tool)

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