Low dose streptozotocin causes stimulation of the immune system and of anti-islet cytotoxicity in mice

Abstract

Multiple low doses of streptozotocin arc known to induce immune-mediated insulin deficient diabetes and depression of immune reactivity. We show here that immune depression by streptozotocin is not general but that some parts of the immune system are stimulated. Spleen cells from streptozotocin-treated mice showed enhanced cytotoxicity against syngeneic islet cells and various tumour cells including insulinoma cells. Several cell types served as effector cells, including macrophages, asialo GM1⁺ and Lyt-2⁺ lymphocytes. The increased cytotoxic activity towards islet cells was mostly due to macrophages and to non-asialo GM1⁺ and non-Lyt-2⁺ lymphocytes. A higher activation state of macrophages in low dose streptozotocin-treated mice was demonstrated by measurements of superoxide anion release. We conclude that multiple low doses of streptozotocin stimulate ‘natural cytotoxicity’, i.e. the non-MHC restricted cytotoxic activity of macrophages, T cells and natural killer lymphocytes.