PT  - JOURNAL ARTICLE
AU  - Gallichan, W. Scott
AU  - Balasa, Balaji
AU  - Davies, Joanna D.
AU  - Sarvetnick, Nora
TI  - Pancreatic IL-4 Expression Results in Islet-Reactive Th2 Cells That Inhibit Diabetogenic Lymphocytes in the Nonobese Diabetic Mouse
DP  - 1999 Aug 01
TA  - The Journal of Immunology
PG  - 1696--1703
VI  - 163
IP  - 3
4099  - http://www.jimmunol.org/content/163/3/1696.short
4100  - http://www.jimmunol.org/content/163/3/1696.full
SO  - J. Immunol.1999 Aug 01; 163
AB  - When immunological tolerance breaks down, autoimmune destruction of insulin-producing β 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.