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Virus-Induced Diabetes in a Transgenic Model: Role of Cross-Reacting Viruses and Quantitation of Effector T Cells Needed To Cause Disease†

By Noemi Sevilla, Dirk Homann, Matthias von Herrath, Fernando Rodriguez, Stephanie Harkins, J. Lindsay Whitton and Michael B. A. Oldstone

Abstract

Virus-specific cytotoxic T lymphocytes (CTL) at frequencies of >1/1,000 are sufficient to cause insulin-dependent diabetes mellitus (IDDM) in transgenic mice whose pancreatic β cells express as “self” antigen a protein from a virus later used to initiate infection. The inability to generate sufficient effector CTL for other cross-reacting viruses that fail to cause IDDM could be mapped to point mutations in the CTL epitope or its COO− flanking region. These data indicate that IDDM and likely other autoimmune diseases are caused by a quantifiable number of T cells, that neither standard epidemiologic markers nor molecular analysis with nucleic acid probes reliably distinguishes between viruses that do or do not cause diabetes, and that a single-amino-acid change flanking a CTL epitope can interfere with antigen presentation and development of autoimmune disease in vivo

Topics: Pathogenesis and Immunity
Publisher: American Society for Microbiology
Year: 2000
OAI identifier: oai:pubmedcentral.nih.gov:111829
Provided by: PubMed Central
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