ABSTRACT
Earlier we had described a dual aetiology diabetes mellitus (DADM) in mice injected with a sub-diabetogenic dose of streptozotocin (SD-SZN) and afterwards infected with coxsackie B3 virus (CBV). Further experiments were conducted to understand the mechanism of diabetogenesis. In in vitro stimulation and proliferation tests, the splenic lymphocytes (SLC) of mice given either SD-SZN or CBV infection showed lower responses to two T cell mitogens than those of control mice, indicating an immunosuppressive effect. Unexpectedly, SLC of mice given both SD-SZN and CBV showed enhanced response, indicating immunoactivation; they were not stimulated to proliferation in response to CBV antigen, indicating that the immunoactivation was not directed against CBV, but against streptozotocin or cellular elements. When mice were depleted of T cells by injecting with anti-thymocyte serum, the diabetogenic effect of SD-SZN and CBV infection was abrogated, without diminishing the replication of virus in the pancreas. Thus beta cell injury in DADM appears to be T cell-mediated.