High Levels of IDO-Expressing CD16+ Peripheral Cells, and Tregs in Graft Biopsies From Kidney Transplant Recipients Under Belatacept Treatment

• Published in: Transplantation proceedings 2010-11, Vol.42 (9), p.3489-3496
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Abatacept; Adult; Antigen-Presenting Cells - drug effects; Antigen-Presenting Cells - enzymology; Antigen-Presenting Cells - immunology; Biological and medical sciences; Biopsy; Cyclosporine - administration & dosage; Female; Flow Cytometry; Forkhead Transcription Factors - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; GPI-Linked Proteins - blood; Humans; Immunoconjugates - administration & dosage; Immunohistochemistry; Immunosuppressive Agents - administration & dosage; Indoleamine-Pyrrole 2,3,-Dioxygenase - blood; Kidney - drug effects; Kidney - immunology; Kidney - pathology; Kidney Transplantation - adverse effects; Male; Medical sciences; Middle Aged; Receptors, IgG - blood; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Time Factors; Tissue, organ and graft immunology; Treatment Outcome
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2010.08.037

Abstract 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.