Immunologic studies of the prediabetic stage in the spontaneous autoimmune diabetes mellitus of the BB rat

Twenty-eight BB diabetes-prone rats underwent prospective analysis to determine levels of circulating Ia antigen-bearing “activated” T lymphocytes prior to 50 days of age using mouse antirat monoclonal antibodies OX6 (anti-Ia) and W3/13 (anti-T-cell) and a fluorescence-activated cell sorter. Pancreatic biopsies were obtained within 48 hrs of lymphocyte sampling and histologically examined for the presence of a lymphocytic infiltrate. Elevated levels of “activated” T lymphocytes (above 4.00%) accurately identified a prediabetic stage and predicted which BB rats would subsequently become diabetic (93% sensitivity). The insulitis lesion occurs in the latter portion of this immunologically defined prediabetic stage just prior to the development of hyperglycemia. This observation suggests that islet cell destruction represents the final focus of a chronic immune response.