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A viral epitope that mimics a self antigen can accelerate but nit initiate autoimmune diabetes

Academic Article
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Overview

authors

  • Christen, U.
  • Edelmann, K. H.
  • McGavern, Dorian
  • Wolfe, T.
  • Coon, B.
  • Teague, M. K.
  • Miler, S. D.
  • Oldstone, Michael
  • von Herrath, M. G.

publication date

  • November 2004

journal

  • Journal of Clinical Investigation  Journal

abstract

  • We document here that infection of prediabetic mice with a virus expressing an H-2Kb-restricted mimic ligand to a self epitope present on beta cells accelerates the development of autoimmune diabetes. Immunization with the mimic ligand expanded autoreactive T cell populations, which was followed by their trafficking to the islets, as visualized in situ by tetramer staining. In contrast, the mimic ligand did not generate sufficient autoreactive T cells in naive mice to initiate disease. Diabetes acceleration did not occur in H-2Kb-deficient mice or in mice tolerized to the mimic ligand. Thus, arenavirus-expressed mimics of self antigens accelerate a previously established autoimmune process. Sequential heterologous viral infections might therefore act in concert to precipitate clinical autoimmune disease, even if single exposure to a viral mimic does not always cause sufficient tissue destruction.

subject areas

  • Animals
  • Autoantigens
  • B-Lymphocytes
  • Blood Glucose
  • CD8-Positive T-Lymphocytes
  • Cytokines
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 1
  • Disease Models, Animal
  • Epitopes
  • Immunohistochemistry
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes
  • T-Lymphocytes, Cytotoxic
  • Time Factors
  • Transgenes
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci200422557

PubMed ID

  • 15520861
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Additional Document Info

start page

  • 1290

end page

  • 1298

volume

  • 114

issue

  • 9

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