Role of Inflammatory Infiltrate in Activation and Effector Function of Cloned Islet Reactive Nonobese Diabetic CD8+ T Cells: Involvement of a Nitric Oxide-Dependent Pathway

摘要: To investigate how CD8+ T cells interact with beta and local inflammatory in islets, we have isolated cell clones from nonobese diabetic (NOD) spleen that recognize destroy both islets the NOD insulinoma line NIT-1. The destroyed pre-existing inflammation better than without signs of inflammation. Islets NOD-scid mice were only poorly, but could be improved by adding IL-7 to assay. Anti-IFN-gamma Abs inhibited destruction infiltrated islets. Single effective stimulators IFN-gamma production cloned cells, which varied >50-fold depending on degree islet infiltration. This effect mononuclear infiltrate mimicked NIT-1 augmented above level stimulated alone. enhancing attributed their macrophage subpopulation was not MHC restricted, although recognition Ag subsequent restricted expressing H-2Db molecules. An inhibitor inducible NO synthase inflamed cells. We propose macrophages provide a form bystander costimulation cell-specific respond producing activates macrophages. Activated facilitate through synthesis-dependent pathway.