Expression of Transgene Encoded TGF-β in Islets Prevents Autoimmune Diabetes in NOD Mice by a Local Mechanism
| Autor: | Richard A. Flavell, Dominic Picarella, Iqbal S. Grewal, F. Susan Wong, Hua Wang, Charles A. Janeway, Kate D. Grewal |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Genetically modified mouse
endocrine system medicine.medical_specialty Adoptive cell transfer endocrine system diseases Transgene medicine.medical_treatment Immunology Apoptosis Mice Transgenic Nod Biology Immune tolerance Islets of Langerhans Mice Mice Inbred NOD Transforming Growth Factor beta Internal medicine Diabetes mellitus Immune Tolerance medicine Animals Insulin Immunology and Allergy Promoter Regions Genetic Pancreas NOD mice medicine.disease Diabetes Mellitus Type 1 Endocrinology Leukocytes Mononuclear |
| Zdroj: | Journal of Autoimmunity. 19:9-22 |
| ISSN: | 0896-8411 |
| Popis: | To analyse the effects of TGF-beta in insulin dependent diabetes mellitus (IDDM), we have developed non-obese diabetic (NOD) transgenic mice expressing TGF-beta under the control of the rat insulin II promoter. Pancreata of TGF-beta transgenic mice were roughly one twentieth of the size of pancreata of wild-type NOD mice and showed small clusters of micro-islets rather than normal adult islets. However, these islets produced sufficient levels of insulin to maintain normal glucose levels and mice were protected from the diabetes, which developed in their negative littermates. A massive fibrosis was seen in the transgenic pancreata that was accompanied with infiltration of mononuclear cells that decreased with age. Interestingly, these mice showed normal anti-islet immune response in their spleens and remained susceptible to adoptive transfer of IDDM by mature cloned CD8 effector cells. TUNEL assays revealed increased apoptosis of invading cells when compared to non-transgenic NOD mice. Taken together, these results suggest that TGF-beta protects islets by a local event. |
| Databáze: | OpenAIRE |
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