Streptozotocin-induced diabetes in mice lacking alphabeta T cells.
Multiple low-dose streptozotocin (MD-STZ) is widely used for the experimental induction of diabetes, but, as non-obese diabetic (NOD)-scid/scid 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 receptor (TCR) alpha-chain were therefore used to assess whether TCR alphabeta+ cells are involved in the diabetogenic effects of MD-STZ injections. Young NOD mice lacking TCR alphabeta cells, when given five daily 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). We 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 alphabeta cells tipping the balance between tolerable and clinically damaging action on islet cells.
Elliott
J I
JI
Transplantation Biology Group, Clinical Sciences Centre, Hammersmith Hospital, London, UK.
Dewchand
H
H
Altmann
D M
DM
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D006943:Hyperglycemia / Q000139:chemically induced / Q000276:immunology; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D010179:Pancreas / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013311:Streptozocin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D013311:Streptozocin