Deficiency of γδT cells protects against abdominal aortic aneurysms by regulating phosphoinositide 3-kinase/AKT signaling

Objective: It is known that T lymphocytes are activated in human abdominal aortic aneurysms (AAAs). gamma delta T cells, as a subset of T cells, play a role in many inflammation-related diseases. However, whether gdT cells participate in the formation of AAA remains unknown. In this study, we explored the role of gamma delta T cells in AAA lesions. Methods and Results: Using the porcine pancreatic elastase-induced AAA model, we found that knock out of gamma delta T cells significantly attenuated AAA formation. To elucidate how gamma delta T cells contribute to AAA, microarray analysis was performed, which found that the phosphoinositide 3-kinase/AKT signaling pathway was activated in elastase-perfused gamma delta T knockout (gamma delta T KO) mice. By studying differentially expressed genes involved in phosphoinositide 3-kinase signaling, we found that proliferation-related genes (Sos1, Mtor, Myc) were upregulated whereas apoptosis-related genes (Pten, Bcl1, Bad) were downregulated in elastase-perfused gamma delta T KO mice. Furthermore, histopathologic analysis showed increased PCNA(+) and decreased TUNEL+ cells in elastase-perfused gamma delta T KO mice compared with wild-type mice. In addition, inflammatory cytokines including interleukin-1 beta, Mcp-1, and tumor necrosis factor-a were downregulated in the aneurysm tissues of elastase-perfused gamma delta T KO mice. Conclusions: These data reveal a pathogenic role of gamma delta T cells in the experimental AAA model, likely through mechanisms regulating cell proliferation and mediating inflammatory response. Thus, targeting of gamma delta T cells may offer a potential therapeutic method for aortic aneurysms.