REGULATORY T CELLS IN ABDOMINAL AORTIC ANEURYSMS


Guo-Ping Shi, M.D., Brigham and Women's Hospital, Boston, MA, USA

Regulator T cells (Tregs) are anti-inflammatory CD4+CD25+Foxp3+ T cells that are impaired in both numbers and activities in human and experimental coronary heart diseases. Abdominal aortic aneurysm (AAA) is an aortic disease that its pathogenesis involves extensive infiltration of pro-inflammatory cells that release pro-inflammatory cytokines to activate vascular cells and other inflammatory cells, thereby leading to arterial wall remodeling, expansion, and rupture. Using immunostaining of human AAA lesions, we found that the numbers of CD4+Foxp3+ Tregs were also reduced in these lesions. ELISA of Treg protein Foxp3 demonstrated significantly lower Foxp3 proteins in plasma cell lysate preparations from patients with AAAs (n=485) than those from age and gender-matched AAA-free controls (n=204) (121.43±46.63 vs. 190.61±39.02 ng/mL, P<0.00001). Pearson’s correlation test (r = –0.147, P=0.007) and multivariate linear regression test (B= –0.013±0.005, P=0.006) demonstrated significant and negative association between plasma cell Foxp3 protein with human AAA annual growth rate. In angiotensin II (Ang-II)-induced AAAs, lesion Foxp3+ Treg numbers were correlated negatively and significantly with the concentrations of Ang-II that was used to infuse apolipoprotein E-deficient (Apoe–/–) mice (r= –0.883, P<0.0001). Increased abdominal aortic diameterd in Ang-II infusion-induced AAAs in Apoe–/– mice can be significantly suppressed if mice received adoptive transfer of in vitro prepared Tregs from wild-type (WT) mice before Ang-II infusion. In contrast, when Tregs from interleukin-10-deficient (Il10–/–) mice were used, these Tregs failed to suppress Ang-II infusion-induced AAAs in Apoe–/– mice, although Foxp3 immunostaining demonstrated similar numbers of Tregs in AAA lesions from Apoe–/– mice between recipient mice received Tregs from WT mice or Il10–/– mice. These observations suggest that Tregs suppress AAA growth by releasing IL10.