title: Prevention of cyclophosphamide-induced diabetes by anti-V beta 8 T-lymphocyte-receptor monoclonal antibody therapy in NOD/Wehi mice.
abstract: Walter & Eliza Hall Institute nonobese diabetic (NOD/Wehi) mice exhibit a low incidence of spontaneous diabetes mellitus, but one large dose of cyclophosphamide (CY) can lead to a rapid progression to overt diabetes. Macrophages and Lyt-2+ and L3T4+ cells have been demonstrated to be involved in beta-cell destruction in this model. The role of a specific subset of T-lymphocytes expressing a particular T-lymphocyte-receptor segment was examined in CY-induced diabetic NOD mice with a mouse anti-V beta 8 T-lymphocyte-receptor monoclonal antibody (F23.1). After administration of CY, only 4 of 51 treated mice became hyperglycemic compared to 23 of 47 untreated mice, 13 of 26 mice treated with an isotype-matched control ascites, and 4 of 6 mice given antibody-negative ascites. Insulitis was significantly reduced in the F23.1-treated group, and immunocytochemistry revealed the absence of V beta 8 expression on cells in the lymphoid organs and insulitis of these mice. This investigation revealed that V beta 8+ cells were implicated in CY-induced diabetes in NOD/Wehi mice.
authors.affiliation: Transplantation Unit, Walter & Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Bacelj
authors.forename: B
authors.initials: B
authors.lastname: Charlton
authors.forename: T E
authors.initials: TE
authors.lastname: Mandel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007124:Immunoenzyme Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D010179:Pancreas / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D003520:Cyclophosphamide