Splenocytes from non-obese-diabetic mice binding to xenogeneic beta-cells in vitro: an early marker of cell-mediated immunity.

In as much as Type 1 diabetes is a T-cell mediated autoimmune disease, the valuation of cell mediated immunity would be useful for the study of its prodromal period. We have previously reported an increased binding of T splenocytes with alpha beta receptors from NOD mice to xenogeneic rat insulinoma (RIN) cells. Our present aim was to study this phenomenon in a large number of NOD mice (n = 243) of both sexes and at different ages, together with insulitis, islet cell antibodies (ICA), and insulin autoantibodies (IAA), in order to assess their respective timing of onset, prevalence, and changes during the natural history of the disease. The number of RIN-adherent splenocytes was higher (p < 0.001) in NOD mice than in several control strains and than in F1 mice (NOD x BALB/c) which did not develop diabetes or insulitis. The increased number of RIN-adherent splenocytes in NOD mice is called "diabetic rosettes", and positivity is defined as a value of RIN-adherent splenocytes higher than the mean+2SD of control mice. The prevalence of "diabetic rosettes" in NOD mice was 56%. Females displayed higher numbers of RIN-adherent splenocytes and a higher prevalence of "diabetic rosettes" (70% vs 45%) than male NOD mice (p < 0.03). Using haematoxylin-eosin staining, marked insulitis became detectable after 30 days of age, with a prevalence reaching 100% after 120 days and a severity which was higher in female than in male mice (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)