Summary. The present study concerns the effect of the experimental diabetogenic encephalomyocarditis (EMC) virus on normal and athymic nude mice of BALB/c origin. The effect of simultaneous immunosuppressive pharmacological treatment with a derivative of cyclophosphamide in a relatively low dose (3 mg/mouse) was also studied. After inoculation with EMC virus, 36% of the normal mice, but none of the nude mice, developed diabetes mellitus and 93% of the normal mice, but none of the nude mice, developed paresis of one or more leg(s). When lower doses of EMC virus were given, few or none of the normal mice developed diabetes or paresis. After treatment with a cyclophosphamide-derivative, the number of paralysed mice increased. EMC virus in abundant amounts could be isolated from the pancreas and heart of all virus-inoculated mice, including the non-diabetic nude mice.Antibodies against EMC virus were found in all groups of virus-inoculated mice, although only in small amounts in nude and immunosuppressed normal mice. Histological examination revealed no significant differences between the islets of Langerhans of the experimental mice, diabetic as well as non-diabetic, and the control mice with respect to lymphocytic infiltration.It is concluded that the thymus-dependent immune system seems to be of decisive importance for the development of diabetes in this virus model.
Key words:Encephalomyocarditis virus, diabetes mellitus, athymic nude mice, the thymus-dependent immune system, cyclophosphamide.This investigation concerns the effect of the experimental diabetogenic encephalomyocarditis (EMC) virus (M-strain) on the athymic nude mouse and on the normal, haired mouse of BALB/c origin. The purpose of the present investigation was to study the importance of the immune system in the development of diabetes in this animal model. Several human investigations have suggested that the immune system might play a pathogenic role in Type 1 (insulin-dependent) diabetes mellims. Many patients with Type 1 diabetes possess humoral auto-antibodies directed against the islet-cell cytoplasm [1] and/or antibodies directed against the surface of the islet B cells [2]. Patients with Type I diabetes often exhibit a positive reaction in the leucocyte migration test using different pancreatic homogenates [3]. Various immunological phenomena have been described, in which Type I diabetic subjects differ from healthy control individuals. For example, there is reduced suppressor cell activity at the time of diagnosis [4], and an increase in the number of K cells [5]. The EMC virus has been shown to be diabetogenic in several mouse strains, with quite large variation within and between strains [6]. Earlier studies in the C57 mouse strain demonstrated a lack of diabetogenic effect by the EMC virus on athymic nude mice, whereas abnormal glucose tolerance curves were obtained from heterozygous littermates, and from homozygous normal mice [71.The present investigation utilized BALB/c mice and included an evaluation of blood glucose, virus studies, ...