Peripheral generation and function of CD4+CD25+ regulatory T cells
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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Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy, 11/2011; , ISBN: 978-953-307-362-0
- "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  . T reg cells exist naturally and are called natural T reg cells expressing CD25 and Foxp3. "
ABSTRACT: Preventing or curing an immune-mediated disease requires functional immune cells, in particular T cells, including helper (CD4+; Th) and cytotoxic (CD8+; Tc) T cells. Based on the type of the antigen presenting cells, the nature of antigens, and the cytokine milieu, CD4+ T cells exhibit high plasticity to differentiate into different subsets with stimulatory or regulatory functions. For instance, Th cells can differentiate into Th1 and Th2 type cells, which produce inflammatory (IL-2, IFN-γ, TNF-α, IL-12) and anti-inflammatory (IL-4, IL-10, and TGF-ß) cytokines, respectively. Th cells can also differentiate into a third type of Th cells designated as Th17 type cell that produces IL-17 and mimics the effects of Th1 cells. Similar to Th cells, Tc can differentiate into Tc1, Tc2, and Tc17 subsets that produce cytokine profiles similar to those produced by Th1, Th2, and Th17 cells, respectively. Under certain condition, Th type cells can also differentiate into a regulatory (Treg) type cell, which produces immunosuppressive cytokines such as TGF-ß and IL-10. Similarly, Th17 and Tc1 type cells can acquire immunoreglatory properties. This article sheds a light on how this T cell plasticity shapes the nature of the immune cell responses to inflammation, infection, and cancer.Immunology Endocrine & Metabolic Agents - Medicinal Chemistry (Formerly Current Medicinal Chemistry - Immunology Endocrine & Metabolic Agents) 05/2009; 9(2):90-105. DOI:10.2174/187152209789000687
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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. "
ABSTRACT: Neisseria meningitidis is commonly carried asymptomatically in the upper respiratory tract and only occasionally invades the bloodstream and meninges to cause disease. Naturally acquired immunity appears protective but the nature of the cellular immune response within the mucosa is uncertain. We show that following in vitro stimulation with N. meningitidis serogroup B (MenB) antigens, approximately 66% of the dividing mucosal CD4(+)CD45RO(+) memory population express the Th1-associated IL18-R while the remainder express CRTH2, a Th2-associated marker. The pro-inflammatory bias of this anti-MenB response is not evident in blood, demonstrating compartmentalization at the induction site; and occurs in the presence or absence of lipopolysacharide indicating that these responses are already fully committed. Depletion of CD25(+) cells reveals suppression of the effector CD4(+) T cell response restricted to the mucosa and most marked in children (i.e. those at greatest risk of disease). Mucosal T-regulatory cell (Treg) activity is partially overcome by blocking the human glucocorticoid-induced TNF receptor (GITR) and is not seen following stimulation with antigens from another mucosal pathogen, influenza virus. Pro-inflammatory, antimeningococcal T cell responses may limit invasive disease at the mucosa but Treg induction while reducing immunopathological damage, may also restrict the effectiveness of the protective response, particularly in children.Cellular Microbiology 05/2007; 9(4):1050-61. DOI:10.1111/j.1462-5822.2006.00851.x · 4.82 Impact Factor
Leonie S Taams