OBJECTIVE: To assess the possible role of proinflammatory CD28- T cells in abdominal aortic aneurysms (AAAs). Animal studies and human tissue studies suggest a role for interferon (IFN)-gamma-producing T cells in the development and progression of AAAs. METHODS AND RESULTS: Fluorescence-activated cells sorter analysis of peripheral blood samples and measurement of AAA size using sonography were performed in 101 AAA patients and 38 healthy controls. Peripheral percentages of CD28- T cells of the CD3+CD4+ and the CD3+CD8+ were enriched in AAA patients with 7.8+/-8.8% and 41.9+/-15.7% compared with healthy controls with 2.2+/-6.1% and 24.9+/-15.5%, respectively (P=0.002 and P<0.001, respectively). Both CD4+CD28- and CD8+CD28- T cells produced large amounts of IFN-[gamma] and perforin. Patients with small AAAs (<4 cm) showed higher peripheral levels of CD4+CD28- T cells than those with larger AAAs (P=0.025). Immunohistological examinations revealed 39.1+/-17.2% CD4+CD28- and 44.0+/-13.8% CD8+CD28- in AAA tissue specimens with inflammatory infiltratestes. CONCLUSIONS: IFN-gamma- and perforin-producing CD28- T cells are present in the periphery and the vessel wall of a majority of AAAs. This observation in humans favors the concept of a T cell-mediated pathophysiology of AAAs, especially during the early development of AAAs.