Pancreatic IL-4 expression results in islet-reactive Th2 cells that inhibit diabetogenic lymphocytes in the nonobese diabetic mouse
| Autor: | W S, Gallichan, B, Balasa, J D, Davies, N, Sarvetnick |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Glutamate Decarboxylase
Receptors Antigen T-Cell alpha-beta T-Lymphocytes Epitopes T-Lymphocyte Mice Transgenic Mice SCID Autoantigens Immunophenotyping Islets of Langerhans Mice Diabetes Mellitus Type 1 Th2 Cells Mice Inbred NOD Immune Tolerance Animals Cytokines Female Interleukin-4 Gene Rearrangement beta-Chain T-Cell Antigen Receptor Pancreas |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 163(3) |
| ISSN: | 0022-1767 |
| Popis: | When immunological tolerance breaks down, autoimmune destruction of insulin-producing beta cells in the pancreas can cause insulin-dependent diabetes mellitus. We previously showed that transgenic nonobese diabetic (NOD) mice expressing IL-4 in the pancreas (NOD-IL-4 mice) were protected from insulitis and diabetes. Here we have characterized the avoidance of pathological autoimmunity in these mice. The absence of disease did not result from a lack of T cell priming, because T cells responding to dominant islet Ags were present. These islet Ag-specific T cells displayed a Th2 phenotype, indicating that Th2 responses could account for the observed tolerance. Interestingly, islet Ag-specific Th1 T cells were present and found to be functional, because neutralization of the Th2 effector cytokines IL-4 and IL-10 resulted in diabetes. Histological examination revealed that NOD-IL-4 splenocytes inhibited diabetogenic T cells in cotransfer experiments by limiting insulitis and delaying diabetes. Neutralization of IL-4 in this system abrogated the ability of NOD-IL-4 splenocytes to delay the onset of diabetes. These results indicate that IL-4 expressed in the islets does not prevent the generation of pathogenic islet responses but induces islet Ag-specific Th2 T cells that block the action of diabetogenic T cells in the pancreas. |
| Databáze: | OpenAIRE |
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