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Islet-specific expression of cxcl10 causes spontaneous islet infiltration and accelerates diabetes development

Academic Article
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Overview

authors

  • Rhode, A.
  • Pauza, M. E.
  • Barral, A. M.
  • Rodrigo, E.
  • Oldstone, Michael
  • von Herrath, M. G.
  • Christen, U.

publication date

  • September 2005

journal

  • Journal of Immunology  Journal

abstract

  • During inflammation, chemokines are conductors of lymphocyte trafficking. The chemokine CXCL10 is expressed early after virus infection. In a virus-induced mouse model for type 1 diabetes, CXCL10 blockade abrogated disease by interfering with trafficking of autoaggressive lymphocytes to the pancreas. We have generated transgenic rat insulin promotor (RIP)-CXCL10 mice expressing CXCL10 in the beta cells of the islets of Langerhans to evaluate how bystander inflammation influences autoimmunity. RIP-CXCL10 mice have islet infiltrations by mononuclear cells and limited impairment of beta cell function, but not spontaneous diabetes. RIP-CXCL10 mice crossed to RIP-nucleoprotein (NP) mice expressing the NP of the lymphocytic choriomeningitis virus in the beta cells had massively accelerated type 1 diabetes after lymphocytic choriomeningitis virus infection. Mechanistically, we found a drastic increase in NP-specific, autoaggressive CD8 T cells in the pancreas after infection. In situ staining with H-2D(b)(NP(396)) tetramers revealed islet infiltration by NP-specific CD8 T cells in RIP-NP-CXCL10 mice early after infection. Our results indicate that CXCL10 expression accelerates the autoimmune process by enhancing the migration of Ag-specific lymphocytes to their target site.

subject areas

  • Animals
  • Autoimmunity
  • CD8-Positive T-Lymphocytes
  • Chemokine CXCL10
  • Chemokines, CXC
  • Chemotaxis, Leukocyte
  • Diabetes Mellitus, Type 1
  • Inflammation
  • Islets of Langerhans
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Transgenic
  • T-Cell Antigen Receptor Specificity
  • Viral Proteins
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 16148094
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Additional Document Info

start page

  • 3516

end page

  • 3524

volume

  • 175

issue

  • 6

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