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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
06:27

Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells

Published on: May 6, 2013

CCR4-bearing T cells participate in autoimmune diabetes

Soon H Kim1, Mary M Cleary, Howard S Fox

  • 1Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

The Journal of Clinical Investigation
|December 5, 2002
PubMed

Insights

Chemokine receptor CCR4 identifies pathogenic autoimmune T cells. Targeting its ligand, macrophage-derived chemokine (MDC), reduces T cell infiltration and prevents autoimmune diabetes development in NOD mice.

Area of Science:

  • Immunology
  • Autoimmunity
  • T cell biology

Background:

  • Chemokine receptor expression on T cells is crucial for migration to inflammatory sites.
  • Identifying specific T cell subsets involved in autoimmune diseases is essential for therapeutic development.

Purpose of the Study:

  • To investigate the role of chemokine receptor CCR4 in T cell pathogenicity during autoimmune disease progression.
  • To determine the involvement of CCR4 ligands, TARC and MDC, in autoimmune T cell recruitment and disease development.

Main Methods:

  • Flow cytometry to analyze CCR4 expression on CD4+ T cells in NOD mice.
  • Detection of CCR4 ligand TARC in pancreatic islets.
  • Administration of antibodies to neutralize MDC and assess its effect on insulitis and diabetes.
  • Transgenic expression of MDC to evaluate its impact on CCR4-bearing cell recruitment and disease acceleration.

Main Results:

  • CCR4 was exclusively expressed on memory CD4+ T cells during disease progression in NOD mice.
  • TARC, a CCR4 ligand, was found in islets of prediabetic mice.
  • Neutralization of MDC significantly reduced CCR4-positive T cells in pancreatic infiltrates, inhibiting insulitis and diabetes.
  • Enhanced MDC expression accelerated clinical disease by increasing CCR4-bearing cell recruitment.

Conclusions:

  • CCR4 marks a pathogenic population of autoimmune T cells.
  • The CCR4-MDC axis plays a critical role in the recruitment of T cells to pancreatic islets.
  • Targeting the CCR4-MDC interaction offers a potential therapeutic strategy for autoimmune diabetes.

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