Requirements for viral-mediated autoimmune diabetes: beta-cell damage and immune infiltration.
The induction of autoimmunity by viruses has been attributed to numerous mechanisms. Coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus (IDDM) in mice resembling the final step of disease progression in humans. Following viral infection, autoreactive lymphocytes are activated through exposure to damaged islets consequently precipitating IDDM. However, the viral and host requirements leading up to this final step have yet to be elucidated. We provide evidence that disease induction requires a pre-existing accumulation of beta-cell specific autoreactive T cells within the pancreas, as well as the infection of islet beta-cells. Therefore, the primary role of CB4 in the development of IDDM is to infect tissue, resulting in the presentation of sequestered islet antigen, the stimulation of preexisting autoreactive T cells, and the initiation of disease.
Horwitz
M S
MS
Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. horwitz@scripps.edu
Fine
C
C
Ilic
A
A
Sarvetnick
N
N
D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000821:virology*; D029822:Enterovirus B, Human / Q000276:immunology*; D005260:Female; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic