Coxsackieviral-mediated diabetes: induction requires antigen-presenting cells and is accompanied by phagocytosis of beta cells

Epidemiological studies have associated coxsackie B virus (CBV) with the development of insulin-dependent diabetes mellitus (IDDM) in humans. Infections of genetically susceptible mice with CBV strain 4 (CB4) induce autoimmune diabetes. Herein, we demonstrate that in mice, CB4 infection of insulin-producing pancreatic β cells does not directly cause β cell death. Instead, we observed the phagocytosis of β cells by macrophages following infection. Further, antigen-presenting cells isolated from CB4-infected mice induced diabetes upon adoptive transfer. Therefore, the specificity of CB4 for infection of β cells leads indirectly to the development of IDDM. This generalized mechanism suggests that macrophages are the initiating pathogenic cell type during virus-mediated autoimmune diabetes and that multiple environmental agents specific for β cells could cause IDDM.