Functional Redundancy of CXCR3/CXCL10 Signaling in the Recruitment of Diabetogenic Cytotoxic T Lymphocytes to Pancreatic Islets in a Virally Induced Autoimmune Diabetes Model

  1. Matthias G. von Herrath1,2
  1. 1Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California
  2. 2Type 1 Diabetes R&D Center, Novo Nordisk Inc., Seattle, Washington
  3. 3Pharmazentrum Frankfurt/Center for Drug Research, Development and Safety, Goethe University Hospital, Frankfurt am Main, Germany
  1. Corresponding author: Matthias G. von Herrath, matthias{at}liai.org.

Abstract

Cytotoxic T lymphocytes (CTLs) constitute a major effector population in pancreatic islets from patients suffering from type 1 diabetes (T1D) and thus represent attractive targets for intervention. Some studies have suggested that blocking the interaction between the chemokine CXCL10 and its receptor CXCR3 on activated CTLs potently inhibits their recruitment and prevents β-cell death. Since recent studies on human pancreata from T1D patients have indicated that both ligand and receptor are abundantly present, we reevaluated whether their interaction constitutes a pivotal node within the chemokine network associated with T1D. Our present data in a viral mouse model challenge the notion that specific blockade of the CXCL10/CXCR3 chemokine axis halts T1D onset and progression.

Footnotes

  • Received October 3, 2012.
  • Accepted February 17, 2013.

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