Abstract 124: Regulatory T Cells Suppress Aortic Aneurysm Growth In Mice Through Local Tissue Changes And Lymph Node Colonization

Abstract

Previous studies have shown that adoptive cell transfer (ACT) of regulatory T cells (Tregs) mitigate AAA growth in mice, however these studies have used a dissection AAA model and have not thoroughly studied Treg function in mice after ACT. Treg suppression of systemic or local inflammation has not been rigorously studied in our model. We therefore sought to evaluate the effects of Treg ACT in mice with a specific focus on Treg migration, colonization, and inflammatory changes within local tissue. Methods: AAA was induced in B57Bl/6 mice expressing the Thy 1.2 allele using a topical elastase + BAPN model (E-BAPN). Heat inactivated elastase (HiE-BAPN) was used as a control. On postoperative day (POD) 2, animals were treated with PBS (E-BAPN-PBS) injection or ACT of 2 million Tregs (E-BAPN-Tregs). CD4+ CD25+ FoxP3+ Tregs used for ACT were isolated from B57Bl/6 mice expressing the Thy 1.1 allele. Mice underwent surveillance ultrasounds (US) weekly to track AAA growth for 42 days. At specific time points mice were sacrificed and aortic diameter was recorded. Aortic tissue and regional lymph nodes were harvested for analysis. Results: Maximum aortic diameter (MAD) by both US and video microscopy was significantly higher in the AAA group (E-BAPN vs. HiE-BAPN; p<.001) with changes observed by POD 7. Mice treated with ACT had significantly reduced MAD (E-BAPN-Tregs vs. E-BAPN-PBS; p<.05) with significant changes identified by POD 21. Thy1.1+ Tregs were detected in the tissue and regional aortic lymph nodes (LN) until day 42 with only a slight declination in the percent Thy1.1 + cells over time. Thy1.1+ Tregs retained phenotypic markers over time. E-BAPN-Treg mice had significantly altered inflammatory markers compared to E-BAPN-PBS mice including local macrophage and T-cell composition as well as inflammatory cytokines. Conclusion: Treg ACT suppress AAA growth in a topical elastase + BAPN mouse model through tissue and LN colonization and alteration of the local inflammatory milieu.