Regulatory T cells in human disease and their potential for therapeutic manipulation

Abstract

Summary Regulatory T cells are proposed to play a central role in the maintenance of immunological tolerance in the periphery, and studies in many animal models demonstrate their capacity to inhibit inflammatory pathologies in vivo. At a recent meeting [Clinical Application of Regulatory T Cells, 7–8 April 2005, Horsham, UK, organized by the authors of this review, in collaboration with the British Society for Immunology and Novartis] evidence was discussed that certain human autoimmune, infectious and allergic diseases are associated with impaired regulatory T‐cell function. In contrast, evidence from several human cancer studies and some infections indicates that regulatory T cells may impair the development of protective immunity. Importantly, certain therapies, both those that act non‐specifically to reduce inflammation and antigen‐specific immunotherapies, may induce or enhance regulatory T‐cell function. The purpose of this review was to summarize current knowledge on regulatory T‐cell function in human disease, and to assess critically how this can be tailored to suit the therapeutic manipulation of immunity.

Coxsackievirus A16 infection stimulates imbalances of T cells in children

“…The Th1/Th2 ratio hypothesis explains cancer, diabetes and pathogenic infection well (17)(18)(19). However, the Th1/Th2 ratio hypothesis also demonstrates limitations in several diseases, including asthma, rheumatoid arthritis and chronic hepatitis B (19)(20)(21). In the present study, the Th1/Th2 balance was affected in children with HFMD.…”

Plasmid-based gene therapy of diabetes mellitus

“…21 Immunity is further controlled by various types of Tr cells. [25][26][27][28] They can be broadly divided into two subsets, that is, the natural Tr cells of CD4 + CD25 + Foxp3 + phenotype, which in humans constitute 2-3% of peripheral blood mononuclear cells and the stimulation-induced (or adaptive) Tr cells identified in various models of inflammation, alloreactivity or autoimmunity. In contrast to natural Tr cells, induced Tr cells probably differentiate from naïve CD4 + CD25 À T cells and act principally by secreting regulatory cytokines, such as TGF-b1 (Th3 cells) or IL-10 and TGF-b1 (Tr1 cells).…”

Molecular Mechanisms of Inflammation-Induced Carcinogenesis

“…Recent studies have shown that autoimmune diseases in human are fundamentally associated with the defective function or increased numbers of CD4 + CD25 + regulatory T cells [41]. Autoimmunity can be characterized as disregulated immune function which will cause reaction to self antigen(s).…”