The Influence of the Major Histocompatibility Complex on Development of Autoimmune Diabetes in RIP-B7.1 Mice
| Autor: | Wei Du, F. Susan Wong, Ian J. Thomas, Li Wen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
Endocrinology Diabetes and Metabolism Mice SCID CD8-Positive T-Lymphocytes medicine.disease_cause Major histocompatibility complex Lymphocyte Depletion Autoimmunity Immune tolerance Major Histocompatibility Complex Islets of Langerhans Mice Mice Inbred NOD MHC class I Internal Medicine medicine Animals NOD mice MHC class II biology Histocompatibility Antigens Class I Histocompatibility Antigens Class II MHC restriction Adoptive Transfer Mice Inbred C57BL Diabetes Mellitus Type 1 Immunology B7-1 Antigen biology.protein CD8 |
| Zdroj: | Diabetes. 54:2032-2040 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.54.7.2032 |
| Popis: | The most important genetic susceptibility factor for type 1 diabetes is encoded in the major histocompatibility complex (MHC). The nonobese diabetic (NOD) mouse, which develops spontaneous diabetes, expresses H-2 g7 comprising the MHC class I molecules K d and D b and the MHC class II molecule I-A g7 . However, neither B6.H-2 g7 mice, in which H-2 g7 is expressed on the C57BL/6 genetic background, nor the nonobese resistant (NOR) mouse, in which H-2 g7 is expressed on a genetic background that is 88% similar to NOD mice, develop diabetes. Immune tolerance can be broken in these diabetes-resistant mice expressing H-2 g7 if the costimulatory molecule B7.1 is present on the islet β cells. This does not occur if only single MHC class I components of the H-2 g7 haplotype are present, such as K d in BALB/c mice or D b in C57BL/6 mice, both of which develop only a low level of diabetes when B7.1 is expressed. The presence of I-A g7 leads to the development of an autoimmune T-cell repertoire, and local costimulation of CD8 T-cells precipitates aggressive diabetes. This implies that a major role of the MHC class II molecules in diabetes is the development of an autoreactive T-cell repertoire. |
| Databáze: | OpenAIRE |
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