Prodromal immune manifestations in EMC-M virus induced diabetes: islet bound and circulating antibodies, and changes in lymphocyte subsets.

The thymus-dependence of the encephalomyocarditis (EMC-M) virus induced diabetes has been demonstrated in comparative studies of normal and immunodeficient mice. Since the lymphocytic infiltration in the islets of Langerhans is modest during the virus infection, we have looked for possible indications of humoral immune mechanisms. Using fluorescence microscopy the presence of immunoglobulins in the islets could be shown 3 days after EMC-M-virus inoculation, gradually disappearing about day 14. The Ig deposit is scattered throughout the islets, but the precise target of Ig's has not been detected. Circulating islet cell surface reactive antibodies were demonstrable from the fourth day until about the third week. This period coincides largely with the period in which Ig deposits were present. Virus antibodies in peripheral blood could not be detected until the fifth day after the virus inoculation, whereas virus could be isolated from the third day. Beginning from day 5, about one third of the mice developed severe hyperglycaemia with blood glucose levels up to 35 mmol/l. Lymphocyte subsets of spleen cells were measured using a fluorescence activated cell sorter. Six days after virus inoculation the mean percentage of Lyt 2-positive (suppressor/cytotoxic) cells decreased below the value for control mice (p less than 0.05), but increased significantly (p less than 0.02) 2 weeks later.