Abstract 15197: Adventitial Lymph Vessels are Instrumental in Regulating T Cell Influx in Atherosclerosis In Apoe-/- Mice
Background During plaque progression, the adventitia has been shown to be progressively enriched in inflammatory cells like T and B cells, mast cells and dendritic cells, as well as cytokines and chemokines. While we and others have demonstrated the impact of various adventitial leukocyte subsets on plaque progression, the exact function of local adventitial lymph vessels still remains to be addressed. We hypothesized that adventitial lymph vessels regulate T cell influx into the adventitia and plaque.
Methods ApoE-/- mice (n=22) received a restrictive collar around the carotid arteries and were fed a 0.25% cholesterol diet to induce plaque formation. Atherosclerotic arteries were stained for lymph vessel presence and their colocalization with inflammatory cells. To study the role of local lymph nodes in vivo, lymph nodes and vessels draining the carotid artery were removed upon collar placement, and 5 weeks after dissection, plaque volume and inflammatory content were analyzed. Additionally, T cell homing towards the adventitia was studied by intra-nodal injection of fluorescently labeled T cells into the draining lymph nodes (n=6) or by intravenous injection (n=8).
Results Lymph vessels were abundantly present in the adventitia of plaques, with T cells in close proximity. Upon lymph node dissection, plaque volume increased by 46% compared to controls (dissection 275091 ± 75146μm3 (n=10) vs. control 126971 ± 26263μm3 (n=12); p<0.05). Concomitantly, T cell content in the adventitia and plaque was increased more than twofold (dissection 5.60 ± 1.12% vs. control 2.49 ± 0.58%; p<0.05). Also, a twofold increase in adventitial lymph vessels was found after dissection (dissection 0.0065 ± 0.0013% vs. control 0.0034 ± 0.0011%; p<0.05), suggesting compensatory lymph-angiogenesis. T cell injection into the draining lymph node compared to distal lymph nodes showed a trend (p=0.06) towards more T cells infiltrating the adventitia upon local injection, suggesting that adventitial lymphoid tissue may locally regulate T cell flux in the adventitia and plaque.
Conclusion The present study showed that local lymph vessels in the adventitia of atherosclerotic plaques are able to modulate plaque development, at least in part by regulating local T cell influx.
- © 2011 by American Heart Association, Inc.