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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
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Cutting edge: Foxp3+CD4+CD25+ regulatory T cells induced by IL-2 and TGF-beta are resistant to Th17 conversion by

Song Guo Zheng1, Juhua Wang, David A Horwitz

  • 1Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine at University of Southern California, Los Angeles, CA 90033, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 21, 2008
PubMed

TGF-beta has pleiotropic effects on T cell differentiation that are determined by other cytokines in the local environment. Whereas IL-2 and TGF-beta induce naive T cells to become forkhead/winged helix transcription factor (Foxp3) positive regulatory cells (iTregs), the combination of IL-6 and TGF-beta induces IL-17-producing cells (Th17). Moreover, IL-6 can use TGF-beta produced by thymus-derived natural regulatory T cells (nTregs) to convert them to Th17 cells. In this study, we report a major difference between iTregs and nTregs. Treatment of iTregs with IL-6 did not affect Foxp3 expression, and their suppressive activity in vitro and in vivo was intact. To explain this difference between nTregs and iTregs, we found that IL-2 and TGF-beta down-regulate IL-6 receptor expression and IL-6 signaling. The resistance of iTregs to Th17 conversion suggests that they can function more effectively than nTregs in an inflammatory milieu and emphasizes the central role of IL-2 in combination with TGF-beta to maintain immunologic homeostasis.

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