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Ex Vivo Expanded Regulatory T Cells Inhibit AAA Progression by Limiting CD4+ and CD8+ T Cell Accumulation in Aortic
Chandrashekhar Dasari1,2, Jose Luis Lopez1,2, Masood Shawyan Jan1,2
1Division Of Vascular and Endovascular Surgery, Department of Surgery, University of California, San Francisco, CA, USA.
Biorxiv : the Preprint Server for Biology
|November 24, 2025
Summary
Regulatory T cell (Treg) therapy shows promise for abdominal aortic aneurysms (AAA). By colonizing lymph nodes, Tregs reduce T cell infiltration, thereby mitigating AAA progression and aortic wall damage.
Area of Science:
- Immunology
- Cardiovascular Research
- Vascular Biology
Background:
- Abdominal aortic aneurysms (AAA) are inflammatory conditions with limited early-stage treatments.
- Regulatory T cells (Tregs) are implicated in AAA pathophysiology.
- Understanding Treg mechanisms is vital for developing effective AAA therapies.
Purpose of the Study:
- To investigate the influence of Tregs on immune cell infiltration in AAA.
- To evaluate the therapeutic potential of Treg cell therapy in a mouse model of AAA.
- To elucidate the mechanism by which Tregs impact AAA progression.
Main Methods:
- Utilized a mouse model of elastase-induced AAA.
- Employed congenic transfer of donor Tregs into AAA mice.
- Quantified AAA progression via ultrasound and image micrometry.
- Analyzed tissue samples using flow cytometry, qRT-PCR, and histological staining.
Main Results:
- Treg therapy reduced elastin degradation and aortic wall enlargement in AAA mice.
- Donor Tregs were detected in draining lymph nodes for at least five weeks.
- Pro-inflammatory CD4+ and CD8+ T cell populations were reduced in AAA mice receiving Treg therapy.
Conclusions:
- Treg therapy mitigates AAA progression by reducing T cell infiltration into the aorta.
- Tregs exert their effect by colonizing draining lymph nodes, not directly within the aortic microenvironment.
- This study highlights the potential of Treg therapy for early-stage AAA.
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