| First Author | Marshall HD | Year | 2015 |
| Journal | Elife | Volume | 4 |
| Pages | e04851 | PubMed ID | 25569154 |
| Mgi Jnum | J:269505 | Mgi Id | MGI:6207946 |
| Doi | 10.7554/eLife.04851 | Citation | Marshall HD, et al. (2015) 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. Elife 4:e04851 |
| abstractText | 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-beta 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-beta signaling suppressed the expression of the high affinity IL-2 receptor alpha 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-betaR signaling, suggesting that TGF-beta 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. |
