Abdominal aortic aneurysms are characterized by destruction of elastin and collagen, transmural inflammatory infiltrate, medial neovascularization, and depletion of medial smooth muscle cells. Current concepts of aneurysm disease emphasize the role of pro-inflammatory cytokines and matrix metalloproteinases to mediate the degradation structural extracellular matrix proteins. We propose that a preponderance of Th-1 T-cells activates degradation of elastin and collagen and exacerbates the disease process. In contrast, we hypothesize that the regulatory effects of Th-2 T-cells exerts an immunoprotective and modulator effect counterbalancing the pro-inflammatory Thl response. We will demonstrate this by characterizing the nature of the cellular immune response at various intervals after induction of experimental AAAs in C57B/L wild-type mice by analyzing Thl/Th2 cytokine profiles after elastase perfusion. We will also evaluate whether elastase-induced AAAs can be enhanced or suppressed in mice with specific gene alterations. Finally, we will determine if CD4+ T lymphocytes constitute the primary effectors cells involved in cellular immunity by studying aneurysm process in B cell efficient mice and in CD8 T cell knock-out mice.
