Impaired immune responses in streptozotocin-induced type I diabetes in mice. Involvement of high glucose
Autor: | R. Rubinstein, Graciela Cremaschi, Alicia Beatriz Motta, Ana María Genaro, Miriam R Wald |
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Rok vydání: | 2008 |
Předmět: |
medicine.medical_specialty
T-Lymphocytes Lymphocyte Immunology Dose-Response Relationship Immunologic Apoptosis Biology Lymphocyte Activation medicine.disease_cause Diabetes Mellitus Experimental Mice Immune system Antigen Diabetes mellitus Internal medicine medicine Animals Immunology and Allergy Cells Cultured Cell Proliferation Autoimmune disease B-Lymphocytes Mice Inbred BALB C Type 1 diabetes medicine.disease Streptozotocin Oxidative Stress Diabetes Mellitus Type 1 Glucose Endocrinology medicine.anatomical_structure Immunoglobulin M Hyperglycemia Immunoglobulin G Animal Studies Female Lipid Peroxidation Mitogens Reactive Oxygen Species Oxidative stress medicine.drug |
Zdroj: | Clinical and Experimental Immunology. 154:235-246 |
ISSN: | 1365-2249 0009-9104 |
Popis: | SummaryDiabetes is widely believed to predispose to serious infections. However, the mechanisms linking diabetes and immunosuppression are not well defined. One potential mediator of the altered defence mechanisms is hyperglycaemia. It has been identified as the main factor contributing to the development of diseases associated with diabetes mellitus. In this study we analyse the immune response in diabetes and the direct effect of hyperglycaemia on T and B lymphocyte reactivity. Diabetes induced an early decrease in IgG levels in the secondary response. However, both primary responses against a T-cell-dependent or independent antigen were affected after 6 months of diabetes induction. T- and B- cell proliferation was only decreased at this time. To gain insight into the potential mechanisms involved, we evaluated the influence of hyperglycaemia over the immune response. Pre-incubation of lymph node and spleen cells in a high glucose (HG) containing medium led to a significant time- and dose-dependent decrease in T- and B-cell proliferation. This effect was associated with the presence of HG-derived supernatants. Still viable cells after HG exposition were able to improve their proliferative response when cultured with the mitogen in a fresh standard medium. HG diminished cell viability, increased apoptosis and induced oxidative stress in lymphocytes. These results indicate that HG concentrations can directly affect lymphoid cell growth. An increase in oxidative stress would be implicated in this deleterious effect. The possibility that prolonged exposure to pathologically HG concentrations would result in the immunosuppressive state observed in diabetes is also discussed. |
Databáze: | OpenAIRE |
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