STREPTOZOTOCIN-INDUCED DIABETES IN MICE LACKING ALPHA-BETA T-CELLS

Multiple low-dose streptozotocin (MD-STZ) is widely used for the exper imental induction of diabetes, but, as non-obese diabetic (NOD)-scid/s cid mice have been found to display enhanced susceptibility to MD-STZ, whether or not the model is genuinely autoimmune and T cell-mediated has been unclear. Mice bearing a targeted mutation of the T cell recep tor (TCR) alpha-chain were therefore used to assess whether TCR alpha beta(+) cells are involved in the diabetogenic effects of MD-STZ injec tions. Young NOD mice lacking TCR alpha beta cells, when given five da ily injections of 40 mg/kg STZ, developed diabetes at low frequency (2 /12), despite the widespread destruction of pancreatic islet cells. By comparison, most normal control mice became hyperglycaemic (12/23). W e conclude that whilst much of the tissue destruction observed in this model is due to the direct toxic effect of STZ, a significant amount is also due to the action of TCR alpha beta cells tipping the balance between tolerable and clinically damaging action on islet cells.