Format

Send to

Choose Destination
See comment in PubMed Commons below
Diabetes. 2007 Jan;56(1):186-96.

Modulating protective and pathogenic CD4+ subsets via CD137 in type 1 diabetes.

Author information

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

Abstract

CD137 (TNFRSF9) is an activation-inducible T-cell costimulatory molecule and a member of the tumor necrosis factor (TNF) receptor superfamily. Cd137 is also a candidate gene (in the Idd9.3 interval) for autoimmune diabetes in NOD mice. Here, we demonstrate that anti-CD137 treatment protects NOD mice from diabetes. Anti-CD137-treated mice are not protected from insulitis and still harbor pathogenic T-cells, as demonstrated by transfer studies. Transfer of CD4(+), but not CD8(+), cells from anti-CD137-treated pre-diabetic NOD mice into NOD-scid mice delayed diabetes onset. Anti-CD137 treatment significantly increased the number of CD4(+)CD25(+) cells, which demonstrated intracellular Foxp3 expression and in vitro suppressive activity. The CD4(+)CD25(+) cell subset from anti-CD137-treated mice transferred complete protection from diabetes, whereas the CD4(+)CD25(-) cell subset offered no significant protection. Anti-CD137 treatment of NOD-scid recipients of diabetic spleen cells, however, hastened the onset of disease, showing that the effect of anti-CD137 treatment depends on the balance of pathogenic and protective cells. These results support a critical role for CD137 acting in the early phase of autoimmune diabetes to enhance regulatory cell production. Disease-associated CD137 alleles are likely ineffectual at stimulating a regulatory T-cell population sufficient to prevent disease.

PMID:
17192481
DOI:
10.2337/db06-0793
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center