|
|
Blood, 1 September 2007, Vol. 110, No. 5, pp. 1603-1606.
Prepublished online as a Blood First Edition Paper on April 26, 2007; DOI 10.1182/blood-2007-01-066258.
Previous Article | Next Article 
Submitted January 4, 2007
Accepted April 17, 2007
Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia
Elena E Solomou*, Katayoun Rezvani, Stephan Mielke, Daniela Malide, Keyvan Keyvanfar, Valeria Visconte, Sachiko Kajigaya, A. John Barrett, and Neal S Young
Hematology Branch, NHLBI, NIH, Bethesda, MD
Light microscopy Core Facility, NHLBI, NIH, Bethesda, MD
* Corresponding author; email: solomoue{at}nhlbi.nih.gov.
Regulatory T-cells are believed to control the development and progression of autoimmunity by suppressing autoreactive T-cells. Decreased numbers of CD4+ CD25+ FOXP3-positive T-cells (Treg) are associated with impaired immune homeostasis and development of autoimmune diseases. The transcription factors FOXP3 and NFAT1 have key roles in regulatory T-cell development and function. Here, we show that Treg are decreased at presentation in almost all patients with aplastic anemia; FOXP3 protein and mRNA levels also are significantly lower in aplastic anemia patients and NFAT1 protein levels are decreased or absent. Transfection of FOXP3-deficient CD4+CD25+ T-cells from patients with a plasmid encoding wild type NFAT1 resulted in increased FOXP3 expression in these cells. By NFAT1 knock-down in CD4+CD25+ T-cells, FOXP3 expression was decreased, when NFAT1 expression is decreased. Our findings indicate that decreased NFAT1 could explain low FOXP3 expression and diminished Treg frequency in aplastic anemia. Treg defects are now implicated in autoimmune marrow failure.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
D. Q. Tran, J. Andersson, D. Hardwick, L. Bebris, G. G. Illei, and E. M. Shevach
Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures
Blood,
May 21, 2009;
113(21):
5125 - 5133.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
U. Oh, G. Blevins, C. Griffith, N. Richert, D. Maric, C. R. Lee, H. McFarland, and S. Jacobson
Regulatory T Cells Are Reduced During Anti-CD25 Antibody Treatment of Multiple Sclerosis
Arch Neurol,
April 1, 2009;
66(4):
471 - 479.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Feng, S. Kajigaya, E. E. Solomou, K. Keyvanfar, X. Xu, N. Raghavachari, P. J. Munson, T. M. Herndon, J. Chen, and N. S. Young
Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro
Blood,
April 1, 2008;
111(7):
3675 - 3683.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Bacigalupo
Aplastic Anemia: Pathogenesis and Treatment
Hematology,
January 1, 2007;
2007(1):
23 - 28.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|