The role of lipid antigen presentation, cytokine balance, and major histocompatibility complex in a novel murine model of adoptive transfer of insulitis

After adoptive transfer of insulitis from nonobese diabetic (NOD) mice, leu kocytes accumulate in the pancreas of SCID/SCID and NOD/SCID mice. These ce lls express classical antigen-presenting molecules and costimulators of T-c ell activation and adhesion molecules involved in homing. The aim of the pr esent study was to study the expression of cytokines involved in regulation of the T-H1/T-H2 balance by these cells, the role of lipid antigen present ation in the local immune system activation in the pancreas during onset of insulitis, and the role of major histocompatibility complex in this proces s. Splenocytes from NOD and BALB/c mice were injected intraperitoneally to SCID/SCID and NOD/SCID mice. Sections from the pancreata of these injected mice were stained for cytokines (tumor necrosis factor alpha [TNF-alpha], i nterferon gamma [IFN-gamma], CD1d, interleukin 2 [IL-2], IL-4, IL-6, IL-10, and IL-12). Some SCID/SCID and NOD/SCID mice injected with NOD splenocytes developed a severe disease, IL-10 was expressed in almost all the animals: in exocrine pancreas, large groups of infiltrating lymphocytes, endothelia of blood vessels, pancreatic islets, and interstitial tissue. CD1d was fou nd in most of the mice: in the endothelia of collecting ducts and blood ves sels of the pancreas, lymphocytic infiltrates, interstitial tissue, septae, islets, and a pancreatic lymph node. TNF-alpha was expressed notably more often in the pancreata of NOD/SCID than SCID/SCID mice. It was found betwee n pancreatic lobules, in the epithelia of collecting ducts, endothelia of b lood vessels, islets, capillaries, infiltrates, and septae. IL-6 was expres sed more in the SCID/SCID than in the NOD/SCID mice. It was seen in infiltr ates, walls of blood vessels, around islets, and in connective tissue. IFN- gamma was found only in the pancreata of SCID/SCID and NOD/SCID mice inject ed with NOD splenocytes. The expression of IL-2 and IL-12 was very scarce. IL-4 was not expressed at all. The present study clearly shows that antigen presentation has a role in the development of autoimmune diseases after ad optive transfer of splenocytes from diseased mice to intact ones and that I L-10 may have a central role in the control of the disease process.