Immune responses of diabetic animals

Abstract

Streptozotocin-induced diabetes in mice was associated with a marked decrease in size and nucleated cell content of the thymus and spleen. Thymocytes were reduced by 96% compared to the number observed in normal age- and sex-matched mice; recovery was not observed within 81 days following Streptozotocin administration. The degree of hyperglycaemia produced by a single dose of Streptozotocin (200mg/kg, IV) in mice 30 days after treatment was inversely related to the percentage of lymphocytes in peripheral blood. The number of nucleated spleen cells remaining 9–81 days after Streptozotocin treatment was 26–47% of the number observed for normal mice. The blastogenic responses of spleen cells from streptozotocin-diabetic mice did not parallel the continued depression in the number of lymphocytes when the number of cells in the in vitro assays was normalised. Spleen cells from 9-day streptozotocin-diabetic mice had depressed thymidine incorporation in mixed lymphocyte culture responses, an in vitro correlate of graft rejection responses induced when allogeneic lymphocytes are cultured together. Spleen cells from 20–81 day Streptozotocin animals did not differ significantly from normal. The generation of cytotoxic effector cells in vitro, however, was depressed for spleen cells obtained from 22- and 48-day Streptozotocin mice. When UV-induced syngeneic tumour fragments were implanted in normal and Streptozotocin mice, the diabetic animals supported the progressive growth of the tumour while normal mice did not. In contrast, Streptozotocin mice that had been lethally irradiated and reconstituted with normal syngeneic bone marrow and spleen cells prevented tumour growth as well as normal control mice. Insulin treatment of Streptozotocin mice (1 unit NPH/day, SC) did not change tumour rejection by diabetic animals, although a recovery in the size of the thymus was observed. These results indicated that Streptozotocin directly depresses some cell-mediated immune responses independent of its diabetogenic actions.