Foxp3 programs the development and function of CD4+CD25+ regulatory T cells

@article{Fontenot2003Foxp3PT,
  title={Foxp3 programs the development and function of CD4+CD25+ regulatory T cells},
  author={Jason D Fontenot and Marc A. Gavin and Alexander Y. Rudensky},
  journal={Nature Immunology},
  year={2003},
  volume={4},
  pages={330-336}
}
CD4+CD25+ regulatory T cells are essential for the active suppression of autoimmunity. [] Key Result CD4+CD25+ regulatory T cells rescue disease development and preferentially expand when transferred into neonatal Foxp3-deficient mice. Furthermore, ectopic expression of Foxp3 confers suppressor function on peripheral CD4+CD25− T cells. Thus, Foxp3 is a critical regulator of CD4+CD25+ regulatory T cell development and function.
Influence of FOXP3 on CD4+CD25+ regulatory T cells
TLDR
How, in humans, the induction of FOXP3 in nonregulatory CD4+ T cells can result in the generation of regulatory T cells in the periphery is discussed, which has implications on both how autoimmunity is regulated in vivo as well an impact on the development of therapeutic interventions for the treatment of autoIMmunity.
Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells.
TLDR
FoxP3 is a crucial regulatory gene for the development and function of CD25(+)CD4(+) regulatory T cells, and can be used as their reliable marker for treatment of autoimmune/inflammatory diseases and negative control of various immune responses.
Induction of Foxp3 demethylation increases regulatory CD4+CD25+ T cells and prevents the occurrence of diabetes in mice
TLDR
The in vivo treatment with DAC can significantly promote the development of natural thymic CD4+CD25+Foxp3+ Treg cells through Foxp3 demethylation, implicating a therapeutic application of DAC in patients suffering from autoimmune diseases.
Analysis of Modulation of Foxp3 Expression in CD4+CD25+ Regulatory Cells from NOD Mice
Abstract CD4+CD25+ regulatory cells control the development of autoimmunity, including type 1 diabetes, and the transcription factor Foxp3 is crucial for the development and function of these cells.
Regulatory CD4+ T Cells Are Crucial for Preventing CD8+ T Cell-Mediated Autoimmunity1
TLDR
An experimental mouse model in which suppressive and helper T cells cannot mediate their functions is developed and demonstrated that regulatory CD4+ T cells play an important direct role in the prevention of peripheral CD8+ T cell-mediated autoimmunity.
Impaired T Cell Receptor Signaling in Foxp3+ CD4 T Cells
Abstract:  Dominant tolerance to autoantigens is primarily achieved through the action of the CD4+CD25+Foxp3+ subset of T cells, which have the capability of suppressing autoreactive T cells that
CD25− T Cells Generate CD25+Foxp3+ Regulatory T Cells by Peripheral Expansion1
TLDR
It is shown that CD25+ cells arising from donor CD25− cells upon homeostatic proliferation in recipient mice express markers of freshly isolated Treg cells, display an anergic state, and suppress the proliferation of other cells in vitro.
Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling
TLDR
It is found that the differentiation, acquisition of functional capacity and formation of a sizeable pool of suppressor T cells in the thymus was independent of interleukin 2 signaling, but that interleukoin 2 was essential for the survival of mature Foxp3+ regulatory T cells.
A critical function for TGF-β signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells
TLDR
It is shown that conditional deletion of transforming growth factor-β receptor I (TβRI) in T cells blocked the appearance of CD4+CD25+Foxp3+ thymocytes at postnatal days 3–5, and paradoxically, beginning 1 week after birth, the same TβRI-mutant mice showed accelerated expansion of thymic CD4+.
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References

SHOWING 1-10 OF 33 REFERENCES
CD25+CD4+ T cells contribute to the control of memory CD8+ T cells
TLDR
It is concluded that CD25+CD4+ T cells are involved in the IL-2-mediated inhibition of memory CD8+ T cell division and that IL-1 controls memory phenotype CD8-T cell numbers at least in part through maintenance of the CD25-CD4- T cell population.
Homeostasis of Peripheral CD4+ T Cells: IL-2Rα and IL-2 Shape a Population of Regulatory Cells That Controls CD4+ T Cell Numbers1
TLDR
It is demonstrated that IL-2Rα is an absolute requirement for the development of the regulatory CD25+CD4+ T cells that control peripheral CD4 T cell homeostasis, while IL- 2 is required for establishing a sizeable population of these cells in the peripheral pools.
Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance
Summary: There is accumulating evidence that T‐cell‐mediated dominant control of self‐reactive T‐cells contributes to the maintenance of immunologic self‐tolerance and its alteration can cause
Homeostasis and anergy of CD4+CD25+ suppressor T cells in vivo
TLDR
It is found that TS cells were hyporesponsive to antigenic stimuli in vivo and unable to flux Ca2+ upon T cell receptor (TCR) engagement, but were not impaired in their proliferative response to lymphopenia, which was dependent on major histocompatibility complex class II expression.
Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide
TLDR
It is shown that interactions with a single self-peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR) to undergo selection to become CD4+CD25+ regulatory T cells.
An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation
TLDR
It is shown that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RBlow population, providing the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.
CD4+CD25+ suppressor T cells: more questions than answers
  • E. Shevach
  • Biology, Medicine
    Nature Reviews Immunology
  • 2002
TLDR
The enhancement of suppressor-cell function might prove useful for the treatment of immune-mediated diseases, whereas the downregulation of these cells might be beneficial for the enhancement of the immunogenicity of vaccines that are specific for tumour antigens.
Origin of regulatory T cells with known specificity for antigen
TLDR
The immunoglobulin κ–controlled expression of an agonist in different cell types correlated with the phenotype of the generated TR cells, and it was found that aberrant expression on thymic stroma yielded predominantly CD4+CD25+TR cells, which—under physiological conditions—may be induced by ectopically expressed organ-specific antigens and thus prevent organ- specific autoimmunity.
Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice.
TLDR
The data indicate that important regulatory interactions occur between the CD45RBhigh and CD45RBlowCD4+ T cell subsets and that disruption of this mechanism has fatal consequences.
...
1
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3
4
...