Interference of the CD30-CD30L pathway reduces atherosclerosis development

Arterioscler Thromb Vasc Biol. 2012 Dec;32(12):2862-8. doi: 10.1161/ATVBAHA.112.300509. Epub 2012 Oct 18.

Abstract

Objective: Costimulatory molecules tightly control immune responses by providing positive signals that promote T-cell activation or by transducing inhibitory signals that limit T-cell responses. CD30 and CD30L are members of the tumor necrosis factor receptor superfamily and are involved in the activation and proliferation of T and B cells, which have been implicated in the initiation and progression of atherosclerosis. In the present study, we thus aimed to determine the role of the CD30-CD30L pathway in the development of atherosclerosis.

Methods and results: Western-type diet-fed low-density lipoprotein receptor-deficient mice were treated with an anti-CD30L antibody for 8 weeks, which resulted in a reduction of atherosclerotic lesion formation in the aortic root by 35%. Reduced numbers of adventitial CD3(+) T cells were found in anti-CD30L-treated mice, whereas no differences were observed in collagen and macrophage content of the atherosclerotic lesions. B-cell and mast cell responses were also not affected on anti-CD30L treatment. Interestingly, splenocyte proliferation was reduced by 53%, whereas T-cell numbers were concomitantly reduced in anti-CD30L-treated mice compared with control mice. These data thus indicate that the CD30-CD30L pathway solely exerts its function via inhibition of T-cell responses.

Conclusions: In the present study, we are the first to show that interruption of the CD30-CD30L pathway reduced initial atherosclerosis development by modulating T-cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / pharmacology
  • Antibodies, Anti-Idiotypic / therapeutic use
  • Atherosclerosis / etiology
  • Atherosclerosis / physiopathology
  • Atherosclerosis / prevention & control*
  • CD30 Ligand / antagonists & inhibitors*
  • CD30 Ligand / drug effects
  • CD30 Ligand / physiology*
  • Cell Proliferation / drug effects
  • Cholesterol, Dietary / adverse effects
  • Dietary Fats / adverse effects
  • Disease Models, Animal
  • Female
  • Ki-1 Antigen / physiology*
  • Mice
  • Mice, Knockout
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Signal Transduction / physiology*
  • T-Lymphocytes / pathology

Substances

  • Antibodies, Anti-Idiotypic
  • CD30 Ligand
  • Cholesterol, Dietary
  • Dietary Fats
  • Ki-1 Antigen
  • Receptors, LDL