Type V collagen-induced oral tolerance plus low-dose cyclosporine prevents rejection of MHC class I and II incompatible lung allografts
| Autor: | Yoshito Yamada, Ichiro Yoshino, Yasuo Sekine, Kazuhiro Yasufuku, Shigetoshi Yoshida, David S. Wilkes, Irina Petrache, David D. Brand, Heather L. Benson |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Graft Rejection
Male medicine.medical_specialty medicine.medical_treatment Immunology Dose-Response Relationship Immunologic Administration Oral chemical and pharmacologic phenomena Biology Rats Inbred WKY Article Immune system Antigen Internal medicine Histocompatibility Antigens Rats Inbred BN medicine Immunology and Allergy Lung transplantation Animals Cells Cultured medicine.diagnostic_test Histocompatibility Testing Histocompatibility Antigens Class II Immunosuppression Ciclosporin Coculture Techniques Histocompatibility Rats Transplantation Bronchoalveolar lavage Endocrinology surgical procedures operative Cyclosporine Drug Therapy Combination Transplantation Tolerance Collagen Type V Immunosuppressive Agents medicine.drug Lung Transplantation |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 183(1) |
| ISSN: | 1550-6606 |
| Popis: | Autoimmunity to type V collagen (col(V)) is a major risk factor for lung allograft rejection. Although col(V)-induced oral tolerance abrogates rejection of minor histoincompatible lung transplants, its ability to prevent rejection of fully MHC incompatible lung allografts is unknown. Rat lung allografts fully incompatible at MHC class I and II loci (Brown Norway (RT1n)) were transplanted into untreated Wistar Kyoto rat recipients (WKY, RT1l), or WKY rats were fed col(V) pretransplantation. To determine whether col(V) enhanced cyclosporine (CsA)-mediated immune suppression, WKY rats were treated with low-dose CsA (5 mg/kg), posttransplant, or oral col(V) plus CsA. The data showed that in contrast to col(V) or CsA, col(V) plus low-dose CsA significantly prevented rejection pathology, down-regulated alloantigen-induced production of IFN-γ and IL-17A, and suppressed chemotaxis for lung macrophages in allograft bronchoalveolar lavage fluid that was associated with lower local levels of MCP-1 (CCL2). Col(V) plus CsA was associated with alloantigen-induced expression of IL-10 in mediastinal lymph node or splenic T cells, intragraft expression of IL-10 and Foxp3 in perivascular and peribronchiolar mononuclear cells, and constitutive production of IL-10 from allograft alveolar macrophages. These data demonstrate that col(V) enhances low-dose CsA-mediated immune suppression, and suggest a role for oral col(V) in immune modulation in lung transplantation. |
| Databáze: | OpenAIRE |
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