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 (i.e., 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 β cells, resulting in IDDM.
Bibliographical noteFunding Information:
This is publication number 6471-NP from the Department of Neuropharmacology, Scripps Clinic and Research Foundation, La Jolla, CA 92037. This work was supported in part by USPHS grants Al69464 (M. 8. A. 0.) AG-64342 (P. S. and M. B. A. 0.) and NS-01330 (M. N.). We thank lain Campbell and Nora Sarvetnick for helpful comments. We acknowledge Sandra Shyp and Tani Minor for excellent technical assistance and Gay Schilling for manuscript preparation.
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