Progression from insulitis to beta-cell destruction in NOD mouse requires L3T4+ T-lymphocytes.
The identity of the cells responsible for beta-cell destruction in type I (insulin-dependent) diabetes is still uncertain. L3T4+ T-lymphocytes have a role in the initiation of insulitis and in damaging transplanted allogeneic islets in nonobese diabetic (NOD) mice. The role of L3T4+ T-lymphocytes in destruction of beta-cells of the NOD mouse was studied in cyclophosphamide (CY)-induced diabetic NOD mice with a rat anti-L3T4 monoclonal antibody (MoAb). After administration of CY, most untreated animals became diabetic, whereas all antibody-treated animals remained normoglycemic. Insulitis was still present in MoAb-treated animals, but immunocytochemical staining showed rat antibody blocking the L3T4 antigen on T-lymphocytes. This study provides further evidence that L3T4+ T-lymphocytes are critical to the process of beta-cell destruction in NOD mice. The means by which L3T4+ cells exert their effect remains to be clarified.
Charlton
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Transplantation Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Mandel
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D000818:Animals; D000911:Antibodies, Monoclonal; D003520:Cyclophosphamide; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D007515:Islets of Langerhans / Q000473:pathology*; D051379:Mice; D013601:T-Lymphocytes / Q000032:analysis / Q000145:classification*
D000911:Antibodies, Monoclonal; D003520:Cyclophosphamide