The Role of IL-10 and TGF-β in the Differentiation and Effector Function of T Regulatory Cells
Abstract
Suppression by T regulatory (Tr) cells is essential for the induction of peripheral tolerance. Many types of CD4+ Tr cells have been described in a number of systems, and although the precise mechanisms which mediate their effects remain to be defined, it is well established that they can suppress immune responses via cell-cell interactions and/or the production of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). Type 1 T regulatory (Tr1) cells are defined by their ability to produce high levels of IL-10 and TGF-β, and these cytokines mediate their ability to suppress pathological immune responses in the settings of transplantation, allergy and autoimmune disease. Tr1 cell activity is not necessarily beneficial, and they can also suppress immune responses to antigens from tumours and pathogens. In vivo, the differentiation of Tr1 cells is likely controlled by certain dendritic cells which promote IL-10 production and may express tolerogenic costimulatory molecules. Another subset of CD4+ Tr cells is defined by constitutive expression of CD25, and although these CD4+CD25+ Tr cells appear to suppress via mechanisms which are largely independent of cytokines, they may actively promote the differentiation of Tr1 cells. Many questions about the basic biology of Tr1 cells remain to be answered, but the development of therapeutic strategies designed to harness their immunoregulatory effects can already be contemplated.
Part of CIRS biomarkers research · Curated by Lauren Lowenstein, The Biotoxin Lady
Key Biomarkers
Cited By (8)
- CD4+CD25bright Regulatory T Cells Actively Regulate Inflammation in the Joints of Patients with the Remitting Form of Juvenile Idiopathic ArthritisThe Journal of Immunology · 2004
- Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cellsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology · 2009
- Plasmodium falciparum–Mediated Induction of Human CD25hiFoxp3hi CD4 T Cells Is Independent of Direct TCR Stimulation and Requires IL-2, IL-10 and TGFβPLoS Pathogens · 2009
- Granulocyte colony‐stimulating factor promotes the generation of regulatory DC through induction of IL‐10 and IFN‐αEuropean Journal of Immunology · 2004
- The characterization and role of regulatory T cells in immune reactionsFrontiers in bioscience · 2008
- Activation-induced FoxP3 in human T effector cells does not suppress proliferation or cytokine productionInternational Immunology · 2007
- Vasoactive intestinal peptide regulates Th17 function in autoimmune inflammationNeuroImmunoModulation · 2007
- T-cell regulatory mechanisms in specific immunotherapyChemical immunology/Fortschritte der Allergielehre/Progress in allergy/Chemical immunology and allergy · 2008
References (5)
- Differential Cytokine Requirements for Regulation of Autoimmune Gastritis and Colitis by CD4+CD25+T CellsJournal of Autoimmunity · 2001
- A Role for TGF-β in the Generation and Expansion of CD4+CD25+ Regulatory T Cells from Human Peripheral BloodThe Journal of Immunology · 2001
- Human CD25+CD4+ T Suppressor Cell Clones Produce Transforming Growth Factor β, but not Interleukin 10, and Are Distinct from Type 1 T Regulatory CellsThe Journal of Experimental Medicine · 2002
- Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells.The Journal of Experimental Medicine · 1996
- Regulation of immune responses by TGF-betaAnnual Review of Immunology · 1998
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