Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response

MBA Oldstone, M Nerenberg, P Southern, J Price… - Cell, 1991 - cell.com
MBA Oldstone, M Nerenberg, P Southern, J Price, H Lewicki
Cell, 1991cell.com
We investigated the potential association between viruses and insulin-dependent(type 1)
diabetes (IDDM) by developing a transgenic mouse model. By inserting into these mice a
unique viral protein that was then expressed as a self-antigen in the pancreatic islets of
Langerhans, we could study the effect on that expressed antigen alone, or in concert with an
induced antiviral (ie, autoimmune) response manifested later in life in causing IDDM. Our
results indicate that a viral gene introduced as early as an animal's egg stage, incorporated …
Summary
We investigated the potential association between viruses and insulin-dependent(type 1) diabetes (IDDM) by developing a transgenic mouse model. By inserting into these mice a unique viral protein that was then expressed as a self-antigen in the pancreatic islets of Langerhans, we could study the effect on that expressed antigen alone, or in concert with an induced antiviral (ie, autoimmune) response manifested later in life in causing IDDM. Our results indicate that a viral gene introduced as early as an animal’s egg stage, incorporated into the germline, and expressed in islet cells does not produce tolerance when the host is exposed to the same virus later in life. We observed that the induced anti-self (viral) CTL response leads to selective and progressive damage of p cells, resulting in IDDM.
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