Insulin in Oral Immune 'Tolerance': A One-Amino Acid Change in the B Chain Makes the Difference
| Autor: | Dirk Homann, Dyrberg, T., Petersen, J., Oldstone, M. B. A., Herrath, M. G. |
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| Rok vydání: | 1999 |
| Předmět: |
Mice
Inbred BALB C Swine Molecular Sequence Data Immunology Administration Oral Adoptive Transfer Peptide Fragments Mice Diabetes Mellitus Type 1 Nucleoproteins Amino Acid Substitution Mice Inbred NOD Organ Specificity Lymphocyte Transfusion Immune Tolerance Animals Humans Insulin Lymphocytic choriomeningitis virus Immunology and Allergy Female Amino Acid Sequence Spleen |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Oral administration of self-Ags can dampen or prevent autoimmune processes by induction of bystander suppression. Based on encouraging results from experiments in nonobese diabetic (NOD) mice, clinical trials have been initiated in type 1 diabetes using human insulin as an oral Ag. However, neither the precise antigenic requirements nor the mechanism of bystander suppression are currently understood in detail. Here we report that 1) a 1-aa difference in position 30 of the insulin B chain abrogated the ability of insulin to confer protection in both NOD as well as a virus-induced transgenic mouse model for type 1 diabetes. In the latter model transgenic mice express the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promotor (RIP) in the pancreatic β cells and develop diabetes only following LCMV infection; and 2) protection could be transferred with insulin B chain-restimulated but not LCMV-restimulated splenocytes from RIP-NP transgenic mice, demonstrating that the mechanism of diabetes prevention in the RIP-NP model is mediated by insulin B chain-specific, IL-4-producing regulatory cells acting as bystander suppressors. |
| Databáze: | OpenAIRE |
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