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 beta cells does not directly cause beta cell death. Instead, we observed the phagocytosis of beta 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 beta 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 beta cells could cause IDDM.
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Marc S
MS
Horwitz
Alex
A
Ilic
Cody
C
Fine
Balaji
B
Balasa
Nora
N
Sarvetnick
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002455:Cell Division / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D029822:Enterovirus B, Human / Q000276:immunology*; D006651:Histocytochemistry; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure / Q000821:virology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000276:immunology
D007328:Insulin