Allograft-Specific Cytokine Profiles Associate with Clinical Outcome After Islet Cell Transplantation
| Autor: | Frans H. J. Claas, Timothy Tree, J H L Velthuis, Daniel Pipeleers, Gabrielle G.M. Pinkse, Dave L. Roelen, P M W van der Meer-Prins, Bart Keymeulen, Bart O. Roep, Pieter Gillard, Gaby Duinkerken, Volkert A L Huurman, Robert Hilbrands |
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| Rok vydání: | 2009 |
| Předmět: |
Lymphocyte
medicine.medical_treatment Islets of Langerhans Transplantation chemical and pharmacologic phenomena T-Lymphocytes Regulatory Cohort Studies Islets of Langerhans Diabetes Mellitus medicine Humans Transplantation Homologous Immunology and Allergy Cytotoxic T cell Pharmacology (medical) Transplantation geography Islet cell transplantation geography.geographical_feature_category business.industry Islet Mixed lymphocyte reaction Interleukin 10 Treatment Outcome medicine.anatomical_structure Cytokine Immunology Cytokines Lymphocyte Culture Test Mixed business T-Lymphocytes Cytotoxic |
| Zdroj: | American Journal of Transplantation. 9:382-388 |
| ISSN: | 1600-6135 |
| Popis: | Islet cell transplantation can cure type 1 diabetes, but allograft rejection and recurrent autoimmunity may contribute to decreasing insulin independence over time. In this study we report the association of allograft-specific proliferative and cytokine profiles with clinical outcome. Peripheral blood mononuclear cells were obtained of 20 islet recipients. Cytokine values in mixed lymphocyte cultures (MLC) were determined using stimulator cells with graft-specific HLA class II. Qualitative and quantitative cytokine profiles were determined before and after islet transplantation, blinded from clinical outcome. Cytotoxic T Lymphocyte precursor (CTLp) assays were performed to determine HLA class I alloreactivity. Allograft-specific cytokine profiles were skewed toward a Th2 or regulatory (Treg) phenotype after transplantation in insulin-independent, but not in insulin-requiring recipients. IFNγ/IL10 ratio and MLC proliferation decreased after transplantation in insulin-independent recipients (p = 0.006 and p = 0.01, respectively). Production of the Treg cytokine IL10 inversely correlated with proliferation in alloreactive MLC (p = 0.008) and CTLp (p = 0.005). Production of IL10 combined with low-MLC reactivity associated significantly with insulin independence. The significant correlation between allograft-specific cytokine profiles and clinical outcome may reflect the induction of immune regulation in successfully transplanted recipients. Islet donor-specific IL10 production correlates with low alloreactivity and superior islet function. |
| Databáze: | OpenAIRE |
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