| Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. | |
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MedLine Citation:
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PMID: 15972448 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation but the immune mechanisms leading to the diverse clinical manifestations of cGVHD remain unknown. In this study, we examined regulatory T cells (Tregs) in 57 transplant recipients (30 with cGVHD and 27 without active cGVHD) and 26 healthy donors. Phenotypic studies demonstrated decreased frequency of CD4+CD25+ T cells in patients with cGVHD compared with patients without cGVHD (P < .001) and healthy individuals (P < .001). Gene expression of Treg transcription factor FOXP3 was reduced in cGVHD patients compared with patients without cGVHD (P = .009) or healthy donors (P = .01). T-cell receptor excision circle (TREC) assays for the evaluation of thymus activity revealed fewer TRECs in both transplant groups compared with healthy donors (P < .001 and P = .02, respectively) although no difference was observed between patients with or without cGVHD (P = .13). When tested in functional assays, Tregs from both patient cohorts and healthy individuals mediated equivalent levels of suppression. Collectively, these studies indicate that patients with active cGVHD have reduced frequencies of Tregs but the function of these cells remains normal. These findings support the development of new strategies to increase the number of Tregs following allogeneic hematopoietic stem cell transplantation to prevent or correct cGVHD. |
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Authors:
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Emmanuel Zorn; Haesook T Kim; Stephanie J Lee; Blair H Floyd; Despina Litsa; Sankari Arumugarajah; Roberto Bellucci; Edwin P Alyea; Joseph H Antin; Robert J Soiffer; Jerome Ritz |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2005-06-21 |
Journal Detail:
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Title: Blood Volume: 106 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-10-05 Completed Date: 2005-11-07 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 2903-11 Citation Subset: AIM; IM |
Affiliation:
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Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult CD4-Positive T-Lymphocytes / immunology*, metabolism* Chronic Disease DNA-Binding Proteins / genetics, metabolism* Female Forkhead Transcription Factors Gene Expression Regulation Graft vs Host Disease / genetics, immunology*, metabolism Hematopoietic Stem Cell Transplantation Humans Immunosuppression Male Phenotype Receptors, Interleukin-2 / metabolism* Thymus Gland / immunology |
| Grant Support | |
ID/Acronym/Agency:
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AI29530/AI/NIAID NIH HHS; HL70149/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Receptors, Interleukin-2 |
| Comments/Corrections | |
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