Characterization of the Role of Major Histocompatibility Complex in Type 1 Diabetes Recurrence after Islet Transplantation
| Autor: | Peter Zucker, Holly Y. Young, Bhagirath Singh, Richard A. Flavell, Anthony M. Jevnikar |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Islets of Langerhans Transplantation
CD1 Major histocompatibility complex Major Histocompatibility Complex Mice Th2 Cells Mice Inbred NOD Recurrence MHC class I Animals Cytotoxic T cell Antigen-presenting cell NOD mice Transplantation MHC class II biology Graft Survival Nuclear Proteins Th1 Cells Diabetes Mellitus Type 1 Immunology Trans-Activators biology.protein Cytokines beta 2-Microglobulin CD8 |
| Zdroj: | Transplantation. 78:509-515 |
| ISSN: | 0041-1337 |
| Popis: | BACKGROUND Major histocompatibility complex (MHC) molecules are essential determinants of beta-cell destruction in type 1 diabetes (T1D). MHC class I- or class II-null nonobese diabetic (NOD) mice do not spontaneously develop autoimmune diabetes and are resistant to adoptive transfer of disease. Both CD4+ and CD8+ T cells are associated with graft destruction after syngeneic islet transplantation. MHC molecules within the graft (i.e., on beta-cells or donor lymphocytes) may influence the interactions between antigen presenting cells and effector T cells and, therefore, the survival outcome of the graft. METHODS Donor islets from NOD mice deficient in one or both of beta2-microglobulin and class II transactivator genes were transplanted into diabetic NOD mice. Immunohistochemistry was performed to identify the phenotype of infiltrating cells and to assess graft insulin production. The presence of cytokines in the grafts was assayed by reverse transcription polymerase chain reaction. RESULTS MHC class II-null islets demonstrated rates of rejection comparable with control wild-type (wt) islets. In contrast, MHC class I- and II-null islets demonstrated indefinite survival (over 100 days). Infiltrates of both failed and surviving grafts were comprised of cytotoxic lymphocytes (CTL), helper T cells, and macrophages. Grafts also showed the presence of both Th1- and Th2-type cytokines (interleukin [IL]-2, IL-4, IL-10, and interferon-gamma), independent of graft status. CONCLUSIONS These results demonstrate the primary importance of MHC class I molecules in the pathogenesis of diabetes recurrence postislet transplantation. Conversely, MHC class II expression is not a necessary mechanistic component of transplant destruction. In addition, these results implicate MHC class I-restricted CTLs but not MHC class II-restricted T cells in disease recurrence. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|