May 31, 2011

Differential effects of regulatory T cells on the initiation and regression of atherosclerosis

Atherosclerosis
A C FoksG H M van Puijvelde

Abstract

Regulatory T cells (Tregs) play an important role in the regulation of T cell-mediated immune responses through suppression of T cell proliferation and cytokine production. In atherosclerosis, a chronic autoimmune-like disease, an imbalance between pro-inflammatory cells (Th1/Th2) and anti-inflammatory cells (Tregs) exists. Therefore, increased Treg numbers may be beneficial for patients suffering from atherosclerosis. In the present study, we determined the effect of a vast expansion of Tregs on the initiation and regression of well-established lesions. For in vivo Treg expansion, LDL receptor deficient (LDLr(-/-)) mice received repeated intraperitoneal injections of a complex of IL-2 and anti-IL-2 mAb. This resulted in a 10-fold increase in CD4(+)CD25(hi)Foxp3(+) T cells, which potently suppressed effector T cells ex vivo. During initial atherosclerosis, IL-2 complex treatment of LDLr(-/-) mice fed a Western-type diet reduced atherosclerotic lesion formation by 39%. The effect on pre-existing lesions was assessed by combining IL-2 complex treatment with a vigorous lowering of blood lipid levels in LDLr(-/-) mice. This did not induce regression of atherosclerosis, but significantly enhanced lesion stability. Our data show diff...Continue Reading

  • References21
  • Citations43

References

  • References21
  • Citations43

Citations

Mentioned in this Paper

Pathologic Cytolysis
LDLR wt Allele
Real-Time Polymerase Chain Reaction
Immune Response
Flow Cytometry
Trichrome Stain Method
T-Lymphocyte
Exertion
Cocoa butter
TBX21 wt Allele

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