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Peripheral generation and function of CD4+CD25+ regulatory T cells

Infection and Immunity Research Group, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NN, UK.
Current topics in microbiology and immunology (Impact Factor: 3.47). 02/2005; 293:115-31. DOI: 10.1007/3-540-27702-1_6
Source: PubMed

ABSTRACT The balance between immunity and tolerance is important to maintain immune homeostasis. Several mechanisms are in place to ensure that the immune response is controlled, such as T cell anergy, apoptosis and immune ignorance. A fourth mechanism of peripheral tolerance is the active suppression by regulatory or suppressor T cells. The existence of suppressor T cells was first described in the early 1970s, but these cells became discredited in the 1980s. The work of Shimon Sakaguchi and others, however, has brought these cells back into the limelight and nowadays research into regulatory/suppressor T cells is a very active field of immunology. Different types of regulatory T cells have been described, including CD4+CD25+ T cells that constitutively express CTLA-4, GITR and Foxp3, TGF-beta producing Th3 cells, IL-10 producing Tr1 cells, and CD8+CD28- T cells. This review will focus on the generation and function of CD4+CD25+ regulatory T cells. CD4+CD25+ regulatory cells were originally described as thymus-derived anergic/suppressive T cells. Recent papers, however, indicate that these cells might also be generated in the periphery. CD4+CD25+ regulatory T cells can be activated by self-antigens and non-self-antigens, and once activated can suppress T cells in an antigen nonspecific manner. Interestingly, the suppressive effects of these cells are not restricted to the adaptive immune system (T and B cells) but can also affect the activation and function of innate immune cells (monocytes, macrophages, dendritic cells). These features make the CD4+CD25+ regulatory T cell subset an interesting target for immunotherapy of chronic inflammatory or autoimmune diseases.

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    • "The suppression of autoreactive T cells is essential for establishment of peripheral tolerance and maintenance of immunological homeostasis, (Vigouroux et al. 2004; Stassen et al. 2004). Natural CD4+CD25+ regulatory T cells (nTregs) of thymus origin, have a high avidity for self-antigens and were shown to link central tolerance to induction of regulatory functions in the periphery (Sakaguchi et al. 1995; Sakaguchi and Sakaguchi 2005; Sakaguchi 2005; Taams and Akbar 2005; Bresson et al. 2006). Natural Treg immunosuppressive functions are antigen independent and are largely under control of the forkhead box p3 transcription factor FOXP3 (Fontenot, Gavin and Rudensky 2003; Hori, Nomura and Sakaguchi 2003). "
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    • "cells, which represent about 5 to 10% of CD4 + T-cells in the steady state, play a central role in immune homeostasis and in preventing autoimmune diseases [18] [19]. T reg cells exist naturally and are called natural T reg cells expressing CD25 and Foxp3. "
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    • "However, this bias also carries the risk of inducing tissue destruction and inflammation that may compromise the integrity of the mucosal barrier and upregulate host receptors that may be exploited by the meningococcus for attachment and invasion (Virji, 1996). It has been suggested that within the mucosa, populations of Treg may be generated or activated to inhibit both naïve and memory CD4 + T cell function and help to control such damage (Kong et al., 1996; Hauben and Roncarolo, 2005; Taams and Akbar, 2005). In the case of the meningococcus , this Treg activity may preclude effective elimination of colonizing bacteria from their mucosal niche. "
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Leonie S Taams