Immunohistochemical Analyses of Pancreatic Macrophages and CD4 and CD8 T Cell Subsets Prior to and Following Diabetes in the NOD Mouse

Abstract

CD4 and CD8 T cells and macrophages have been implicated as cellular mediators of beta cell destruction in insulin-dependent diabetes mellitus (IDDM). The ratios of the two T cell subsets were, therefore, quantified in nonobese diabetic (NOD) mouse islets prior to IDDM, at the onset of the disease, and following onset by immunohistochemistry. The number of periislet-, intraislet-, and exocrine-located macrophages were also determined during these stages. At all time points studied (day 90, day 250, at diabetes onset, 4-6 weeks after diabetes), CD4 cells were 2.5 times higher than CD8 cells except at day 250, on which the CD4:CD8 ratio was 3.8. At days 90 and 250, islets were heavily infiltrated with both the T cell subsets associated with lower numbers of macrophages. At onset of the disease and after insulin treatment, although the CD4:CD8 ratios were similar, the absolute numbers of the two subsets were reduced-considerably. At these stages a majority of the islets was atrophied, some were still surrounded by T cells and macrophages and were enriched with glucagon cells. CD4 and CD8 cells were also observed in the exocrine region at the two stages. Macrophages located in the periislet areas were significantly higher in number than in the intraislet positions in all study groups (p = 0.001). They also showed a gradual decline from day 90 to clinical diabetes. Periislet-located macrophages were significantly higher at day 90 than after onset and in control Swiss mice (p < 0.05). The numbers of macrophages in the exocrine areas were similar in all groups of NOD mice. In control Swiss mice they were significantly lower in the periislet, intraislet, and exocrine regions.