scholarly journals 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 ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Heather D Marshall ◽  
John P Ray ◽  
Brian J Laidlaw ◽  
Nianzhi Zhang ◽  
Dipika Gawande ◽  
...  
Keyword(s):  
T Cells ◽  
Transforming Growth Factor Beta ◽  
Cd4 T Cells ◽  
Transforming Growth Factor ◽  
Antibody Responses ◽  
T Follicular Helper Cells ◽  
High Affinity ◽  
Tfh Cells ◽  
Helper Cells ◽  
Follicular Helper

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.

scholarly journals Mucosal T follicular helper cells in SIV-infected rhesus macaques: contributing role of IL-27

2019 ◽  
Vol 12 (4) ◽  
pp. 1038-1054 ◽  
Author(s):  
Félicien Moukambi ◽  
Henintsoa Rabezanahary ◽  
Yasmina Fortier ◽  
Vasco Rodrigues ◽  
Julien Clain ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
T Follicular Helper Cells ◽  
Mesenteric Lymph Nodes ◽  
Tfh Cells ◽  
Helper Cells ◽  
Follicular Helper ◽  
Memory Cd4 T Cells

AbstractMesenteric lymph nodes (MLNs), that drain the large and small intestine, are critical sites for the induction of oral tolerance. Although depletion of CD4 T cells in the intestinal lamina propria is a hallmark of HIV infection, CD4 T cell dynamics in MLNs is less known due to the lack of accessibility to these LNs. We demonstrate the early loss of memory CD4 T cells, including T follicular helper cells (Tfh) and a remodeling of MLN architecture in SIV-infected rhesus macaques (RMs). Along with the loss of Tfh cells, we observe the loss of memory B cells and of germinal center B cells. Tfh cells display a Th1 profile with increased levels of the transcription factors that negatively impact on Tfh differentiation and of Stat5 phosphorylation. MLNs of SIV-infected RMs display lower mRNA transcripts encoding for IL-12, IL-23, and IL-35, whereas those coding for IL-27 are not impaired in MLNs. In vitro, IL-27 negatively impacts on Tfh cells and recapitulates the profile observed in SIV-infected RMs. Therefore, early defects of memory CD4 T cells, as well of Tfh cells in MLNs, which play a central role in regulating the mucosal immune response, may have major implications for Aids.

scholarly journals Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells

2011 ◽  
Vol 208 (5) ◽  
pp. 987-999 ◽  
Author(s):  
Laura M. Fahey ◽  
Elizabeth B. Wilson ◽  
Heidi Elsaesser ◽  
Chris D. Fistonich ◽  
Dorian B. McGavern ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infection ◽  
Cd4 T Cells ◽  
Viral Infections ◽  
Viral Persistence ◽  
Cd4 T Cell ◽  
T Follicular Helper Cells ◽  
Helper Cells ◽  
Follicular Helper

CD4 T cell responses are crucial to prevent and control viral infection; however, virus-specific CD4 T cell activity is considered to be rapidly lost during many persistent viral infections. This is largely caused by the fact that during viral persistence CD4 T cells do not produce the classical Th1 cytokines associated with control of acute viral infections. Considering that CD4 T cell help is critical for both CD8 T cell and B cell functions, it is unclear how CD4 T cells can lose responsiveness but continue to sustain long-term control of persistent viral replication. We now demonstrate that CD4 T cell function is not extinguished as a result of viral persistence. Instead, viral persistence and prolonged T cell receptor stimulation progressively redirects CD4 T cell development away from the Th1 response induced during an acute infection toward T follicular helper cells. Importantly, this sustained CD4 T cell functionality is critical to maintain immunity and ultimately aid in the control of persistent viral infection.

scholarly journals Divergent Expression of CXCR5 and CCR5 on CD4+ T Cells and the Paradoxical Accumulation of T Follicular Helper Cells during HIV Infection

2017 ◽  
Vol 8 ◽  
Author(s):  
John Zaunders ◽  
Yin Xu ◽  
Stephen J. Kent ◽  
Kersten K. Koelsch ◽  
Anthony D. Kelleher
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
T Follicular Helper Cells ◽  
Helper Cells ◽  
Follicular Helper
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