Sub-Areas to Treg cells:
T Cell Suppression
(2)
T Cell Homeostasis
(1)
Costimulation
(0)
Ag-derived
(1)
DC-induced
(1)
Virus-induced
(1)
FoxP3
(3)
TGF-beta-secretion
(3)
TNF-alpha
(1)
(Journal Article): Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
Fontenot JD, Gavin MA, Rudensky AY (Howard Hughes Medical Institute, Department of Immunology, University of Washington, Box 357370, Seattle, WA 98195, USA.)
IN:
Nat Immunol
2003; 4(4):330-336
Impact Factor(s) of Nat Immunol: 27.011 (2005), 27.586 (2004), 28.18 (2003), 27.868 (2002), 17.431 (2001)
ABSTRACT: CD4+CD25+ regulatory T cells are essential for the active suppression of autoimmunity. Here we report that the forkhead transcription factor Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is required for their development. The lethal autoimmune syndrome observed in Foxp3-mutant scurfy mice and Foxp3-null mice results from a CD4+CD25+ regulatory T cell deficiency and not from a cell-intrinsic defect of CD4+CD25- T cells. 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.
TYPE OF PUBLICATION: Original article
Articles citing this article:
|
||
(Journal Article): A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis.
Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG (DNAX Research Institute of Molecular and Cellular Biology, Inc., Human Immunology Department, Palo Alto, California 94304-1104, USA.)
IN:
Nature
1997; 389(6652):737-742
Impact Factor(s) of Nature: 29.273 (2005), 32.182 (2004), 30.979 (2003), 30.432 (2002), 27.955 (2001)
ABSTRACT: Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such active suppression. Here we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RB(high) splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.
TYPE OF PUBLICATION: Original article
Articles citing this article:
|
||
(Journal Article): The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality.
Taylor PA, Lees CJ, Blazar BR (University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis 55455, USA.)
IN:
Blood
2002; 99(10):3493-3499
Impact Factor(s) of Blood: 9.782 (2004), 10.12 (2003), 9.631 (2002), 9.273 (2001)
ABSTRACT: Immune regulatory CD4(+)CD25(+) cells play a vital role in the induction and maintenance of self-tolerance and the prevention of autoimmunity. Recently, CD4(+)CD25(+) cells have been shown to be required for the ex vivo induction of tolerance to alloantigen via costimulatory blockade and to inhibit allogeneic skin graft rejection. Data presented here demonstrate that CD4(+)CD25(+) cells play an important role in graft-versus-host disease (GVHD) generation. Depletion of CD4(+)CD25(+) cells from the donor T-cell inoculum or in vivo CD25-depletion of the recipient before transplantation resulted in increased GVHD mediated by CD4(+) or whole T cells in several strain combinations irrespective of the total body irradiation conditioning regime. The infusion of freshly purified donor CD4(+)CD25(+) cells modestly inhibited GVHD when administered in equal numbers with whole CD4(+) cells. Because CD4(+)CD25(+) cells only account for 5% to 10% of the total CD4(+) population, the administration of high numbers of fresh donor CD4(+)CD25(+) cells may not be clinically practical. However, we found that large numbers of CD4(+)CD25(+) cells can be obtained by ex vivo activation and expansion. Cultured CD4(+)CD25(+) cells, administered in equal numbers with CD4(+) T cells or CD25-depleted whole T cells, resulted in significant inhibition of rapidly lethal GVHD. To our knowledge, this study is the first to demonstrate that activated, cultured CD4(+)CD25(+) cells can offer substantial protection in a relevant in vivo animal model of disease. These data have important ramifications for clinical bone marrow and solid organ transplantation. CD4(+)CD25(+) cells warrant consideration as an exciting new modality of cellular therapy for the inhibition of undesirable autologous and allogeneic responses.
TYPE OF PUBLICATION: Original article
Articles citing this article:
|
||
|
||