Expression and immune response to islet antigens following treatment with low doses of streptozotocin in H-2d mice
Autor: | Frank Buckingham, Elizabeth Baumann, Vaiva Vezys, Kevan C. Herold |
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Rok vydání: | 1997 |
Předmět: |
Male
endocrine system medicine.medical_specialty endocrine system diseases Immunology Biology Streptozocin Diabetes Mellitus Experimental Interferon-gamma Islets of Langerhans Mice Immune system Antigen Internal medicine Diabetes mellitus medicine Immunology and Allergy Animals Antigens Autoimmune disease geography Mice Inbred BALB C Mice Inbred C3H geography.geographical_feature_category nutritional and metabolic diseases Streptozotocin Islet medicine.disease Immunity Innate Transplantation Mice Inbred C57BL Endocrinology Female Interleukin-4 Insulitis medicine.drug |
Zdroj: | Journal of autoimmunity. 10(1) |
ISSN: | 0896-8411 |
Popis: | Insulin dependent diabetes mellitus (IDDM) is likely to be due to the immunologic destruction of the islets of Langerhans. However, the relative importance of expression of a unique set of islet antigens or of differences in immune responses to those antigens in determining susceptibility to auto-immune diabetes is unknown. To a large extent, the reason for this uncertainty is the difficulty in directly identifying islet antigens expressed in vivo. We have studied the relationship between islet antigen expression, immune responsiveness to islet antigens, and the development of diabetes in diabetes induced by multiple low-doses of streptozotocin (STZ) in mice of the H-2dhaplotype. We identified the expression of relevant islet antigens by testing the ability of STZ treated islets to induce tolerance to diabetes in C57BL/KsJ mice after intrathymic transplantation. C57BL/KsJ but not BALB/cByJ mice developed hyperglycaemia and insulitis following STZ treatment. Interferon-γ transcription was detected in intrapancreatic lymphocytes from C57BL/KsJ mice but at lower levels in cells from BALB/cByJ. IL-4 levels were higher in BALB/cByJ than C57BL/KsJ. Intrathymic STZ-treated islets from syngeneic mice induced tolerance to diabetes in C57BL/KsJ mice following transient depletion of mature peripheral T cells, but islets from resistant BALB/cByJ mice did not induce tolerance to disease in C57BL/KsJ mice even though they did cause tolerance to the alloantigens. (C57BL/KsJ×BALB/cByJ)F1 mice developed hyperglycaemia like the susceptible parent following STZ treatment, and islets from these mice induced tolerance to MDSDM when treated with STZ and transplanted intrathymically into C57BL/KsJ. We conclude the expression of islet antigens and the intrapancreatic responses to STZ treated islets differs between mice that are susceptible and resistant to multi-dose streptozotocin induced diabetes mellitus. |
Databáze: | OpenAIRE |
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