Plasticity of T-cell phenotype and function: the T helper type 17 example
Article first published online: 17 NOV 2009
© 2009 Blackwell Publishing Ltd
Volume 129, Issue 2, pages 147–153, February 2010
How to Cite
Peck, A. and Mellins, E. D. (2010), Plasticity of T-cell phenotype and function: the T helper type 17 example. Immunology, 129: 147–153. doi: 10.1111/j.1365-2567.2009.03189.x
- Issue published online: 7 JAN 2010
- Article first published online: 17 NOV 2009
- Received 19 August 2009; revised 16 September 2009; accepted 21 September 2009.
- regulatory T cells;
- T cells
Mature T helper type 1 (Th1) and Th2 cells antagonize the development of the opposing subset to sustain lineage-specific responses. However, the recent identification of a third distinct subset of helper T cells – the Th17 lineage – collapses the established Th1/Th2 dichotomy and raises intriguing questions about T-cell fate. In this review, we discuss the Th17 subset in the context of the effector and regulatory T-cell lineages. Initial studies suggested reciprocal developmental pathways between Th17/Th1 subsets and between Th17/regulatory T-cell subsets, and identified multiple mechanisms by which Th1 and Th2 cells antagonize the generation of Th17 cells. However, recent observations reveal the susceptibility of differentiated Th17 cells to Th1 polarization and the enhancement of Th17 memory cells by the Th1 factors interferon-γ and T-bet. In addition, new data indicate late-stage plasticity of a subpopulation of regulatory T cells, which can be selectively induced to adopt a Th17 phenotype. Elucidating the mechanisms that undermine cross-lineage suppression and facilitate these phenotype shifts will not only clarify the flexibility of T-cell differentiation, but may also shed insight into the pathogenesis of autoimmunity and cancer. Furthermore, understanding these phenomena will be critical for the design of immunotherapy that seeks to disrupt lineage-specific T-cell responses and may suggest ways to manipulate the balance between pathogenic and regulatory lymphocytes for the restoration of homeostasis.