Abstract
The functional repertoire of T cells in abdominal aortic aneurysm (AAA) and the exact nature of aortic wall adaptive cellular immune responses still remains a matter of debate. In this study, we sought to determine whether type 1 or type 2 responses occur predominantly in human aneurysmal aortic lesions. We first examined the phenotype and cytokine secretion profile of T lymphocytes freshly isolated from aneurysmal aortic wall for comparison with their circulating counterparts using flow cytometry. We found that both populations of infiltrating CD4(+) and CD8(+)T cells displayed a unique activated memory phenotype. In addition, we identified the presence in human aneurysmal aortic lesion of CD4(+)T cells producing high levels of interferon (IFN)-gamma but not interleukin (IL)-4, reflecting their type 1 nature. Quantitative analysis of cytokine gene expression confirmed increased IFN-gamma transcript levels in infiltrating cells compared to controls. We next analysed aortic wall responses using LightCycler-based quantitative real-time reverse transcription-polymerase chain reaction. Compared to control non-diseased aortic samples, we demonstrated that whole AAA tissues exhibited high mRNA levels of IFN-gamma but not IL-4. Overexpression of the transcription factor T-bet in the absence of significant GATA-3 expression further assessed the type 1 polarization of aortic wall immune responses. These findings indicate that type 1 CD4(+)T cells predominate in human AAA lesions. This study has important implications for the pathogenesis of aneurysm disease. Through the production of IFN-gamma, T cells may indeed contribute to orchestrate extracellular matrix remodelling.