In this study induction of diabetes in CD1 mice using Coxsackie B4 virus was attempted with a view to developing an adequate animal model. However, in a series of three experiments no diabetic-like state was observed. In clinical studies insulin-dependent diabetics (I.D.D.), insulin-independent diabetics (I.I.D.), and control subjects were tested for leucocyte migration inhibition against pancreatic antigens, Coxsackie virus, and rat liver mitochondria. Inhibition of migration was observed more often against these antigens in the I.D.D. In another study of cell-mediated function lymphocytes from 10 I.D.D. were tested for PHA-induced transformation. Two patients showed depression of this response compared to individual control responses. An indirect immunofluorescence technique was used to assess the incidence of autoantibodies. In 54 I.D.D. islet cell antibodies were found in 32%, whilst there was a greater incidence of other autoantibodies (thyroid, gastric parietal cell, antinuclear, reticulin, smooth muscle and mitochondrial) in the sera of this group compared to I.I.D. and the control subjects. Preliminary absorption studies of islet cell antibody (ICA) positive sera from 4 I.D.D. incubated with Coxsackie B4 virus produced a decrease in intensity of fluorescence in 3 cases, whilst an increase in the intensity was observed in some cases when pancreatic homogenate, microsomes, and mitochondria were used. HLA studies revealed a higher incidence of HLA-B8 and B15 in I.D.D. with a protective effect conferred by HLA-B7. No correlation was found between any HLA antigens and immune phenomena. Finally, 13 I.D.D. were examined for T-cell cytotoxicity against chicken erythrocytes coated with pancreatic fractions, and 17 I.D.D. for antibody-dependent cell-mediated (K-cell) cytotoxicity. No evidence of T-cell cytotoxicity was found, whilst 4/17 patients showed depression of K-cell activity by more than 10% when compared to control subjects.
|Date of Award||1979|