Human CD4+ Memory T Cells Can Become CD4+IL-9+ T Cells

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Human CD4+ Memory T Cells Can Become CD4+IL-9+ T Cells

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Title: Human CD4+ Memory T Cells Can Become CD4+IL-9+ T Cells
Author: Popoola, Joyce; Putheti, Prabhakar; Awasthi, Amit; Gao, Wenda; Strom, Terry Barton

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Citation: Putheti, Prabhakar, Amit Awasthi, Joyce Popoola, Wenda Gao, and Terry B. Strom. 2010. Human CD4+ memory T cells can become CD4+IL-9+ T cells. PLoS ONE 5(1): e8706.
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Abstract: Background: IL-9 is a growth factor for T- and mast-cells that is secreted by human Th2 cells. We recently reported that IL-4+TGF-β directs mouse CD4+CD25−CD62L+ T cells to commit to inflammatory IL-9 producing CD4+ T cells. Methodology/Principal Findings: Here we show that human inducible regulatory T cells (iTregs) also express IL-9. IL-4+TGF-β induced higher levels of IL-9 expression in plate bound-anti-CD3 mAb (pbCD3)/soluble-anti-CD28 mAb (sCD28) activated human resting memory CD4+CD25−CD45RO+ T cells as compared to naïve CD4+CD25−CD45RA+ T cells. In addition, as compared to pbCD3/sCD28 plus TGF-β stimulation, IL-4+TGF-β stimulated memory CD4+CD25−CD45RO+ T cells expressed reduced FOXP3 protein. As analyzed by pre-amplification boosted single-cell real-time PCR, human CD4+IL-9+ T cells expressed GATA3 and RORC, but not IL-10, IL-13, IFNγ or IL-17A/F. Attempts to optimize IL-9 production by pbCD3/sCD28 and IL-4+TGF-β stimulated resting memory CD4+ T cells demonstrated that the addition of IL-1β, IL-12, and IL-21 further enhance IL-9 production. Conclusions/Significance: Taken together these data show both the differences and similarities between mouse and human CD4+IL9+ T cells and reaffirm the powerful influence of inflammatory cytokines to shape the response of activated CD4+ T cells to antigen.
Published Version: doi:10.1371/journal.pone.0008706
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