Prevention of Cyclophosphamide-Induced Diabetes by Anti-Vβ8 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 β-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-Vβ8 T-lymphocyte–receptor monoclonal antibody (F23.1). After administration of CY, only 4 of 51 treated mice became hyperglycemie 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 Vβ8 expression on cells in the lymphoid organs and insulitis of these mice. This investigation revealed that Vβ8+ cells were implicated in CY-induced diabetes in NOD/ Wehi mice.