Insulin-Dependent Diabetes in the Nod Mouse Model II. β Cell Destruction in Autoimmune Diabetes is a TH2and not A TH1Mediated Event
| Autor: | Janet G. Cornelius, Jeffrey T. Anderson, Ammon B. Peck, Alyssa J. Jarpe, William E. Winter |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male medicine.medical_treatment Molecular Sequence Data Immunology Biology Islets of Langerhans Mice Immune system Mice Inbred NOD medicine Animals Immunology and Allergy RNA Messenger B cell NOD mice Autoimmune disease Mice Inbred C3H Base Sequence T-Lymphocytes Helper-Inducer medicine.disease Disease Models Animal Diabetes Mellitus Type 1 medicine.anatomical_structure Cytokine Mice Inbred CBA Cytokines Female Beta cell Insulitis CD8 |
| Zdroj: | Autoimmunity. 15:113-122 |
| ISSN: | 1607-842X 0891-6934 |
| Popis: | Type I, insulin-dependent diabetes (IDD) in both man and animals results from a specific autoimmune destruction of the pancreatic beta cells involving both humoral and cellular immune mechanisms. The pathognomonic histologic lesion, termed insulitis, is an inflammatory and immune cell infiltrate of the pancreatic islet cells. While recent histological and flow cytometric analyses have identified the cell composition of the infiltrate, the presence of a cell population may not reflect the functional reactivities important for beta cell destruction. In the present study, we have investigated the possible functional reactivities of islet-infiltrating mononuclear cell populations by measuring increased cytokine mRNA usage. Results indicate that 1) cytokine mRNA profiles exhibited by islet-infiltrating cells of female and male NOD mice were quite similar with the exception of IL-6 expression and the marked differences in the levels of IL-2 receptor and IL-1 alpha mRNA, 2) CD4+ T lymphocytes expressed IL-4, presumably IL-5, and occasionally IL-10 mRNA but no detectable IL-2 mRNA, 3) CD8+ T lymphocytes exhibited TNF-beta, perforin and high levels of IFN-gamma, and 4) IL-7 was expressed in the islet at very high levels. These findings, together with our earlier flow cytometric analyses of the islet-infiltrating cells, have permitted construction of a detailed model for the natural history of autoimmune diabetes. Interestingly, this model, based on a TH2- and not a TH1-mediated scheme, questions the more popular concepts currently thought to form the bases of the autoimmune reactions underlying IDD. |
| Databáze: | OpenAIRE |
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