tetano
Editor, Senior Moderator
Elife. 2015 Jan 8;4. doi: 10.7554/eLife.04851. [Epub ahead of print]
[h=1]The tumor 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.[/h] Marshall HD[SUP]1[/SUP], Ray JP[SUP]1[/SUP], Laidlaw BJ[SUP]1[/SUP], Zhang N[SUP]1[/SUP], Gawande D[SUP]1[/SUP], Staron MM[SUP]1[/SUP], Craft J[SUP]1[/SUP], Kaech SM[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] T follicular helper cells; TGF-beta; antibody; cytokines; immunology; mouse; viral infection
PMID: 25569154 [PubMed - as supplied by publisher] Free full text
http://www.ncbi.nlm.nih.gov/pubmed/25569154
[h=1]The tumor 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.[/h] Marshall HD[SUP]1[/SUP], Ray JP[SUP]1[/SUP], Laidlaw BJ[SUP]1[/SUP], Zhang N[SUP]1[/SUP], Gawande D[SUP]1[/SUP], Staron MM[SUP]1[/SUP], Craft J[SUP]1[/SUP], Kaech SM[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] T follicular helper cells; TGF-beta; antibody; cytokines; immunology; mouse; viral infection
PMID: 25569154 [PubMed - as supplied by publisher] Free full text
http://www.ncbi.nlm.nih.gov/pubmed/25569154