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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
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Modulating protective and pathogenic CD4+ subsets via CD137 in type 1 diabetes

Junichiro Irie1, Yuehong Wu, Kritika Kachapati

  • 1Division of Rheumatology and Immunology, University of Pittsburgh School of Medicine, PA, USA.

Diabetes
|December 29, 2006
PubMed

Insights

Anti-CD137 treatment protects NOD mice from autoimmune diabetes by enhancing regulatory T-cell production. This immunotherapy shows promise for type 1 diabetes, but its effectiveness depends on the immune cell balance.

Area of Science:

  • Immunology
  • Autoimmune Diseases
  • T-cell Biology

Background:

  • CD137 (TNFRSF9) is a T-cell costimulatory molecule implicated in autoimmune diabetes.
  • The Idd9.3 interval in NOD mice contains candidate genes for autoimmune diabetes, including CD137.

Purpose of the Study:

  • To investigate the role of CD137 in the development of autoimmune diabetes in NOD mice.
  • To determine the therapeutic potential of anti-CD137 treatment in preventing or delaying diabetes onset.

Main Methods:

  • Treatment of NOD mice with anti-CD137 antibodies.
  • T-cell transfer studies using CD4(+) and CD8(+) cells from treated mice into NOD-scid recipients.
  • Analysis of immune cell populations, including CD4(+)CD25(+)Foxp3(+) regulatory T-cells, and their suppressive activity.

Main Results:

  • Anti-CD137 treatment protected NOD mice from diabetes but not insulitis.
  • Transfer of CD4(+) cells from treated mice delayed diabetes onset.
  • Increased CD4(+)CD25(+)Foxp3(+) regulatory T-cells with enhanced suppressive activity were observed in treated mice.
  • Disease onset was hastened when anti-CD137 was administered to recipients of diabetic spleen cells, indicating a balance-dependent effect.

Conclusions:

  • CD137 plays a critical role in the early phase of autoimmune diabetes by promoting regulatory T-cell production.
  • Anti-CD137 immunotherapy holds potential for treating type 1 diabetes, contingent on the balance between pathogenic and protective immune cells.
  • Disease-associated CD137 alleles may be insufficient for generating adequate regulatory T-cell responses to prevent autoimmune diabetes.

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