Dual-Label Immunohistochemical Study of Interleukin-4-and Interferon-γ-Expressing Cells within the Pancreas of the NOD Mouse During Disease Acceleration with Cyclophosphamide

Beta cell destruction has been shown to occur when rodent or human islets are exposed in vitro to inflammatory cytokines, such as interleukin-1β″ (IL-1β), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Other cytokines such as interleukin-4 (IL-4) or inter-leukin-10 (IL-10), when given to NOD mice, prevent insulin-dependent diabetes mellitus (IDDM). In this study, we have employed immunofluorescence histochemistry to study the expression of IFN-γ and IL-4 in the pancreas of female NOD mice at various time-points (days 0, 4, 7, 11 and at onset of diabetes) following disease acceleration with cyclophosphamide (Cy). Dual-label confocal and light microscopy were employed to determine the precise cellular sources of the two cytokines. IL-4 immunolabelling was observed in a few immune cells at days 0, 4, and 7 within the pancreatic islets but in larger numbers at day 11 and at onset of diabetes. The cytokine was co-localized predominantly in CD4 cells, while only a small minority of CD8 cells and mac...