TY - JOUR
T1 - Requirements for viral-mediated autoimmune diabetes
T2 - β-cell damage and immune infiltration
AU - Horwitz, Marc S.
AU - Fine, Cody
AU - Ilic, Alex
AU - Sarvetnick, Nora
N1 - Funding Information:
We would like to thank Cecile King, and Michelle Krakowski for many helpful discussions, Enrique Rodriquez and Lorraine Mocnik for technical assistance. M. Horwitz was a recipient of an American Diabetes Association Career Development Award. N. Sarvetnick was supported by a Diabetes Interdisciplinary Research Program grant from the Juvenile Diabetes Foundation International. This is manuscript number 13661-IMM from The Scripps Research Institute.
PY - 2001
Y1 - 2001
N2 - 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 β-cell specific autoreactive T cells within the pancreas, as well as the infection of islet β-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.
AB - 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 β-cell specific autoreactive T cells within the pancreas, as well as the infection of islet β-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.
KW - Coxsackievirus
KW - Insulin-dependent diabetes mellitus
KW - T lymphocytes
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U2 - 10.1006/jaut.2000.0486
DO - 10.1006/jaut.2000.0486
M3 - Article
C2 - 11334485
AN - SCOPUS:0034979274
SN - 0896-8411
VL - 16
SP - 211
EP - 217
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 3
ER -