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DNA immunization to prevent autoimmune diabetes

Academic Article
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Overview

authors

  • Coon, B.
  • An, L. L.
  • Whitton, J. Lindsay
  • von Herrath, M. G.

publication date

  • July 1999

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Mice expressing lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) as a transgene in their beta cells develop insulin-dependent diabetes mellitus (IDDM) only after LCMV infection. Inoculation of plasmid DNA encoding the insulin B chain reduced the incidence of IDDM by 50% in this model. The insulin B-chain DNA vaccination was effective through induction of regulatory CD4 lymphocytes that react with the insulin B chain, secrete IL-4, and locally reduce activity of LCMV-NP-autoreactive cytotoxic T lymphocytes in the pancreatic draining lymph node. In contrast, similar vaccination with plasmids expressing the LCMV viral ("self") protein did not prevent IDDM, because no such regulatory cells were induced. Thus, DNA immunization with plasmids expressing self-antigens might constitute a novel and attractive therapeutic approach to prevent autoimmune diseases, if the antigens are carefully preelected for an ability to induce regulatory lymphocytes in vivo.

subject areas

  • Animals
  • Diabetes Mellitus, Type 1
  • Immunization
  • Insulin
  • Interleukin-4
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Nucleocapsid Proteins
  • Nucleoproteins
  • T-Lymphocytes, Cytotoxic
  • Vaccines, DNA
  • Viral Core Proteins
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci7209

PubMed ID

  • 10411548
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Additional Document Info

start page

  • 189

end page

  • 194

volume

  • 104

issue

  • 2

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