High levels of IDO-expressing CD16+ peripheral cells, and Tregs in graft biopsies from kidney transplant recipients under belatacept treatment.
Transplant Proc
; 42(9): 3489-96, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-21094802
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme that suppresses T-lymphocyte activity. Costimulation blockade through CTLA4lg increases IDO in antigen-presenting cells. The suppressive effect of IDO is thought to be mediated by Foxp3+CD4+CD25+ regulatory T-cells (Tregs). OBJECTIVE: In this descriptive study, we evaluated the percentage of IDO-expressing peripheral cell subpopulations as well as Tregs in 27 stable kidney transplant recipients receiving either belatacept (LEA29Y), a daughter compound of abatacept (CTLA4lg; n = 19) or cyclosporine (n = 8). METHODS: Blood samples were obtained at 24 ± 2 months (belatacept) and 23 ± 6 months (cyclosporine) of treatment. Intracellular IDO was analyzed by flow cytometry in CD14+, CD11c+, CD16+, CD56+, and CD8+ cell subpopulations. Tregs were assessed by intracellular Foxp3 detection in CD4+CD25+ cells. CD3+, CD4+, CD8+, CD20+, CD68+, IDO+, and Foxp3+ cells were evaluated by immunohistochemistry on graft biopsies obtained preimplantation, at 12 months posttransplant, and in subjects with dysfunction during the first 12 months. RESULTS: Only percentages of CD16+/IDO+-expressing peripheral monocytes were significantly increased among the group receiving belatacept. No differences were observed in peripheral Tregs between the groups. In contrast, higher percentages of Tregs, CD4+, CD8+, and CD68+ cells were noted in dysfunction and at 12 months vs baseline among graft biopsies in subjects receiving belatacept, and also among dysfunction cohorts of belatacept vs Cyclosporine treatment. CONCLUSION: Patients receiving belatacept showed greater amounts of peripheral blood CD16+/IDO+ cells and Tregs on graft biopsies than those under cyclosporine treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
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Ciclosporina
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Receptores de IgG
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Linfócitos T Reguladores
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Imunoconjugados
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Indolamina-Pirrol 2,3,-Dioxigenase
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Imunossupressores
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Rim
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Células Apresentadoras de Antígenos
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Transplant Proc
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Estados Unidos