Interference of the CD30–CD30L Pathway Reduces Atherosclerosis Development
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.
Conclusion—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.
- Received May 3, 2012.
- Accepted October 9, 2012.
- © 2012 American Heart Association, Inc.