Natural and induced regulatory T cells: targets for immunotherapy of autoimmune disease and allergy

Abstract

Recent advances in immunology have greatly increased our understanding of immunological tolerance. In particular, there has been a resurgence of interest in mechanisms of immune regulation. Immune regulation refers to the phenomenon, previously known as immune suppression, by which excessive responses to infectious agents and hypersensitivities to otherwise innocuous antigens such as self antigens and allergens are avoided. We now appreciate that various distinct cell types mediate immune suppression and that some of these may be induced by appropriate administration of antigens, synthetic peptides and drugs of various types. The induction of antigen specific immunotherapy for treatment of autoimmune and allergic diseases remains the 'holy grail' for treatment of these diseases. This goal comes ever closer as understanding of the mechanisms of immune suppression and in particular antigen specific immunotherapy increases. Here we review evidence that immune suppression is mediated by various different subsets of CD4 T cells.

Fig. (1)

CD4+ regulatory T cells. The thymus generates both CD25− and CD25+ Treg cells. T cells respond to antigen presented by mature dendritic cells by differentiating into effector T cells (Teff), secreting cytokines and providing help for B cells and cytotoxic T cells. Antigen presented by immature dendritic cells drives the differentiation of CD25− cells, such as IL-10+ Treg cells, that suppress effector cell generation. Thymus-derived CD25+ Treg cells block expansion of the effector cell population. CD25+FoxP3+ Treg cells can also be generated from CD25− precursors in peripheral lymphoid tissues following repeated encouter of antigen presented by immature DC. Both these and other regulatory populations depend on the production of cytokines, such as IL-10 and TGF-beta, for suppression in vivo, although the requirement for cytokines depends on the nature of the effector T cell response.