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High levels of IDO-expressing CD16+ peripheral cells, and Tregs in graft biopsies from kidney transplant recipients under belatacept treatment.
Furuzawa-Carballeda, J; Lima, G; Uribe-Uribe, N; Avila-Casado, C; Mancilla, E; Morales-Buenrostro, L E; Pérez-Garrido, J; Pérez, M; Cárdenas, G; Llorente, L; Alberú, J.
Afiliação
  • Furuzawa-Carballeda J; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Ciclosporina / Receptores de IgG / Linfócitos T Reguladores / Imunoconjugados / Indolamina-Pirrol 2,3,-Dioxigenase / Imunossupressores / Rim / Células Apresentadoras de Antígenos Tipo de estudo: Clinical_trials Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Transplant Proc Ano de publicação: 2010 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Ciclosporina / Receptores de IgG / Linfócitos T Reguladores / Imunoconjugados / Indolamina-Pirrol 2,3,-Dioxigenase / Imunossupressores / Rim / Células Apresentadoras de Antígenos Tipo de estudo: Clinical_trials Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Transplant Proc Ano de publicação: 2010 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos