Mechanisms of immune suppression by interleukin-10 and transforming growth factor-β: the role of T regulatory cells
Article first published online: 14 MAR 2006
Volume 117, Issue 4, pages 433–442, April 2006
How to Cite
Taylor, A., Verhagen, J., Blaser, K., Akdis, M. and Akdis, C. A. (2006), Mechanisms of immune suppression by interleukin-10 and transforming growth factor-β: the role of T regulatory cells. Immunology, 117: 433–442. doi: 10.1111/j.1365-2567.2006.02321.x
- Issue published online: 14 MAR 2006
- Article first published online: 14 MAR 2006
- Received 26 September 2005; revised 25 November 2005; accepted 25 November 2005.
- allergen-specific immunotherapy;
- T-cell tolerance;
- transforming growth factor-β;
- T regulatory cells
Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific type 1 regulatory (Tr1) cells and T helper (Th) 2 cells appears to be decisive in the development of allergy. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific interleukin-4 (IL-4)-secreting T cells in allergic individuals. Allergen-specific immunotherapy can induce specific Tr1 cells that abolish allergen-induced proliferation of Th1 and Th2 cells, as well as their cytokine production. Tr1 cells utilize multiple suppressor mechanisms, such as IL-10 and transforming growth factor-β (TGF-β) as secreted cytokines and various surface molecules, such as cytotoxic T-lymphocyte antigen 4 and programmed death-1. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors, which depend on CD28 costimulation. IL-10 inhibits CD28 tyrosine phosphorylation, preventing the binding of phosphatidylinositol 3-kinase p85 and consequently inhibiting the CD28 signalling pathway. In addition, IL-10 and TGF-β secreted by Tr1 cells skew the antibody production from immunoglobulin E (IgE) towards the non-inflammatory isotypes IgG4 and IgA, respectively. Induction of antigen-specific Tr1 cells can thus re-direct an inappropriate immune response against allergens or auto-antigens using a broad range of suppressor mechanisms.