Studies on Autoimmunity For Initiation of β-Cell Destruction: V. Decrease of Macrophage-Dependent T Lymphocytes and Natural Killer Cytotoxicity in Silica-Treated BB Rats
- Laboratory of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre, and the Division of Virology, Department of Microbiology and Infectious Diseases, Faculty of Medicine, The University of Calgary, Health Sciences Centre, Calgary Alberta, Canada
- Address correspondence and reprint requests to Dr. Ji-Won Yoon, Department of Microbiology and Infectious Diseases, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Administration of silica, which is selectively toxic to macrophages, to young BB rats resulted in the prevention of insulitis and diabetes. However, the mechanism leading to the prevention of an autoimmune process in silica-treated BB rats is not known. This study was undertaken to investigate the mechanism involved in prevention of insulitis and diabetes. Neonates of diabetes-prone BB (DPBB) rats injected with concanavalin A (ConA)-activated spleen cells from silica-treated DPBB (STDPBB) rats did not develop insulitis or diabetes, whereas DPBB neonates injected with ConA-activated spleen cells from the untreated DPBB rats developed both insulitis and diabetes. Not only was there a decrease of natural killer (NK) cell activity in splenocytes from STDPBB rats, but there was also a significant reduction in the number of immunocytes such as T lymphocytes (helper/inducer and cytotoxic/suppressor) and NK cells. The number of macrophages in both spleen and peripheral blood was significantly decreased in STDP rats compared with untreated DP rats. In contrast to the changes in T lymphocytes and NK cell activity, there was no change in target β-cells in STDPBB rats with regard to the susceptibility to adoptive transfer of insulitis. It is concluded that the prevention of insulitis and diabetes in STDPBB rats is due to a decrease in macrophage-dependent T lymphocytes and NK cell cytotoxicity.
- Received June 7, 1989.
- Revision received December 21, 1989.
- Accepted December 21, 1989.
- Copyright © 1990 by the American Diabetes Association