LYMPHOCYTE VACCINATION PROTECTS PREDIABETIC NONOBESE DIABETIC MICE FROM DEVELOPING DIABETES-MELLITUS

In the therapeutic manoeuvre termed ''lymphocyte vaccination'', activa ted lymphocytes capable of transferring an autoimmune disease are inst ead attenuated and given in vaccine form. We have previously shown tha t such a therapy administered to non-obese diabetic (NOD) mice at 6 we eks of age prevents diabetes mellitus. To assess whether this therapy has potential clinical relevance, in the present study lymphocyte vacc ination was applied in NOD mice in 3 weekly doses commencing ill the i mmediate prediabetic period (age 12 weeks), When insulitis is advanced and diabetes incipient. Of 30 NOD mice receiving active vaccine (comp osed of attenuated lymphocytes from diabetic NOD mice) 13 remained non -diabetic to the age of in comparison with 2 of 30 (6.7%; p < 0.01) mi ce receiving a control vaccine (composed of attenuated lymphocytes fro m tron-diabetic NOD/B10 mice) and 5 of 26 (19.2%; p < 0.01) mice recei ving saline carrier alone. Moreover, in an additional group of 10 NOD mice receiving active vaccine weekly between 12 and 30 weeks, a remain ed diabetes free at the end of the treatment. The most notable effect of the vaccine was that the delay in diabetes onset was accompanied by a reduction in insulitis and in some cases a complete absence of infi ltrating lymphocytes at 30 weeks of age. Immunocytochemistry indicated that when present, islet infiltrating lymphocytes in non-diabetic mic e that received active vaccine showed significantly reduced staining f or interferon-gamma, compared with the infiltrate seen in diabetic mic e receiving the control vaccine or saline. This study demonstrates tha t the rapid progression to diabetes typically seen in 12-week-old NOD mice can be delayed by lymphocyte vaccination, supporting the possibil ity that a vaccine composed of attenuated autologous peripheral blood lymphocytes could be effective in high risk first degree relatives of patients with insulin dependent diabetes mellitus.