Lymphocyte antibodies have been described in autoimmune disorders, inc
luding insulin-dependent diabetes mellitus (IDDM). We have developed a
quantitative method to measure autoantibodies directed against T-lymp
hocytes, based on two-color fluorescence labeling of Wistar mononuclea
r cells and analysis of fluorescence by flow cytometry. The lymphocyte
antibody levels were determined retrospectively in the serum of 73 BB
and 18 Wistar rats. We demonstrated the binding of the lymphocyte aut
oantibodies of both CD4(+) and CD8(+) T-cells. Lymphocyte antibodies w
ere present in 90% of the BB rats at diabetes onset, compared with 11%
of the Wistar rats. At 75 days of age, 83% of the BB rats, which late
r became diabetic, were positive for the lymphocyte antibodies, compar
ed with 15% of their littermates who maintained a normal glucose toler
ance. In all cases, the antibodies were of the immunoglobulin M isotyp
e. We conclude that lymphocyte antibodies are present before diabetes
onset and, using this method, that their presence can predict the deve
lopment of diabetes with a sensitivity of 83% and a specificity of 85%
in BB rats.