MRC National Institute for Medical Research, London
Science for Health
TGF-beta reprograms effector T cell differentiation
31 October 2008
CD4+ helper T cells differentiate into functionally distinct subsets after encountering antigen. T helper 1 (Th1), Th2, Th17 and TGF-beta-induced regulatory T cells (iTreg cells) comprise the currently known helper T cell subsets.
Gitta Stockinger (pictured), from NIMR's Division of Molecular Immunology, and collaborators in Belgium and Germany have shown that there may be yet more effector T cell subsets in addition to the established Th1, Th2 and Th17 effector T cells. A distinct population of CD4 helper T cells characterized by production of interleukin-9 differentiated from naïve precursors in response to IL-4 and TGF-beta. While there is as yet no definite proof that such a subset develops in vivo, the data also showed that existing fully differentiated Th2 cells could be re-programmed to a 'Th9' phenotype upon exposure to TGF-beta.
Previous research has focused on factors that determine lineage commitment of effector T cells and has shown that following a certain number of cell divisions polarization to either Th1 or Th2 seems irreversible. Our results confirm the Th1-Th2 dichotomy, but suggest that there may be more plasticity in effector T cell subsets than previously anticipated. Furthermore, such plasticity is more prevalent between effector programs that are functionally related, such as Th2 and 'Th9' - possibly to allow fine-tuning of immune responses. At the center of the plasticity between Th2 and Th9 programs is TGF-beta, a cytokine with an astonishing range of functions in the immune sytem, adding yet another job description for this versatile cytokine
Gitta Stockinger
Original article
The research findings are published in full in:
Marc Veldhoen, Catherine Uyttenhove, Jacques van Snick, Helena Helmby, Astrid Westendorf, Jan Buer, Bruno Martin, Christoph Wilhelm & Brigitta Stockinger.
Transforming growth factor-β reprograms the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset
Nature Immunology , Epub ahead of print Publisher abstract
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