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Published on: July 1, 2011
Analysis of CD154 and CD40 expression in native coronary atherosclerosis and transplant associated coronary artery
M J Szabolcs1, P J Cannon, U Thienel
1Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Insights
Activated T cells expressing CD154 interact with CD40 on various cells, contributing to coronary atherosclerosis (CA) and transplant-associated coronary artery disease (TCAD) by promoting inflammation.
Area of Science:
- Immunology
- Cardiovascular Pathology
- Cell Biology
Background:
- T cells play a role in coronary atherosclerosis (CA) and transplant-associated coronary artery disease (TCAD).
- The precise mechanisms of T cell interactions within these vascular lesions remain unclear.
- CD154, a T cell molecule, interacts with CD40 on target cells, inducing pro-inflammatory responses.
Purpose of the Study:
- To investigate the potential involvement of CD154-CD40 interactions in the pathogenesis of CA and TCAD.
- To examine the expression patterns of CD154 and CD40 in human coronary artery lesions.
Main Methods:
- Immunohistochemical analysis of CD154 and CD40 expression on coronary artery sections from patients with CA and TCAD.
- Utilized four distinct anti-CD154 monoclonal antibodies (mAbs).
- Performed dual immunolabeling to assess co-expression of CD40 with CD54 (ICAM-1) and CD106 (VCAM-1).
Main Results:
- CD154 expression was localized to infiltrating lymphocytes in both CA and TCAD lesions.
- CD40 was significantly upregulated on intimal endothelial cells, foam cells, macrophages, and smooth muscle cells in both disease types.
- CD40, CD54, and CD106 expression levels correlated significantly with disease severity and the number of intimal lymphocytes.
Conclusions:
- Activated CD154-expressing T cells and CD40-expressing cells are present in CA and TCAD lesions.
- CD154-mediated interactions with CD40+ cells may contribute to the development of CA and TCAD.
- These findings highlight a potential therapeutic target for managing vascular inflammation in these conditions.
Abstract:
T cells have roles in the pathogenesis of native coronary atherosclerosis (CA) and transplant-associated coronary artery disease (TCAD). The mechanisms by which T cells interact with other cells in these lesions are not fully known. CD154 is an activation-induced CD4+ T cell surface molecule that interacts with CD40+ target cells, including macrophages and endothelial cells, and induces the production of pro-inflammatory molecules, including CD54 (ICAM-1) and CD106 (VCAM-1). To investigate whether CD154-CD40 interactions might be involved in the pathogenesis of CA or TCAD we performed immunohistochemical studies of CD154 and CD40 expression on frozen sections of coronary arteries obtained from cardiac allograft recipients with CA (n=10) or TCAD (n=9). Utilizing four different anti-CD154 mAb we found that CD154 expression was restricted to infiltrating lymphocytes in CA and TCAD. CD40 expression was markedly up-regulated on intimal endothelial cells, foam cells, macrophages and smooth muscle cells in both diseases. Dual immunolabeling demonstrated many CD40+ cells co-expressed CD54 and CD106. The extent of CD40, CD54 and CD106 expression showed statistical significant correlation with the severity of disease and the amount of intimal lymphocytes. Together these studies demonstrate the presence of activated CD154+ and CD40+ cells in both CA and TCAD lesions and suggest that CD154-mediated interactions with CD40+ macrophages, foam cells, smooth muscle cells and/or endothelial cells may contribute to the pathogenesis of these diseases.
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