The Journal of Experimental Medicine
Aegean Conferences: 2009 Conferences
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Published online 8 May 2006 doi:10.1084/jem.20052205
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 5, 1273-1282
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ARTICLE

 Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent

Elena Galkina1,4, Alexandra Kadl4, John Sanders3,4, Danielle Varughese4, Ian J. Sarembock3,4, and Klaus Ley1,2,4

1 Department of Biomedical Engineering, 2 Department of Molecular Physiology and Biological Physics, 3 Department of Internal Medicine, and 4 Robert M. Berne Cardiovascular Research Center, University of Virginia, Health Sciences Center, Charlottesville, VA 22908

CORRESPONDENCE Klaus Ley: klausley{at}virginia.edu

Atherosclerosis is an inflammatory disease of large arteries. Flow cytometry of aortic cell suspensions showed that B and T lymphocytes and some macrophages and dendritic cells are already present in the adventitia of normal/noninflamed mouse aortas. Adoptively transferred lymphocytes constitutively homed to the aorta and resided within the adventitia up to 7 d after transfer. Lymphocyte trafficking into normal/noninflamed or atherosclerosis-prone aortas was partially L-selectin dependent. Antigen-activated dendritic cells induced increased T lymphocyte proliferation within the aorta 72 h after adoptive transfer. During progression of atherosclerosis in apolipoprotein-E–deficient mice, the total number of macrophages, T cells, and dendritic cells, but not B cells, increased significantly. This alteration in immune cell composition was accompanied by the formation of tertiary lymphoid tissue in the adventitia of atherosclerotic aortas. These results demonstrate that lymphocytes already reside within the normal/noninflamed aorta before the onset atherosclerosis as a consequence of constitutive trafficking. Atherosclerosis induces the recruitment of macrophages and dendritic cells that support antigen presentation.

Abbreviations used: Ab, antibody; ApoE–/–, apolipoprotein-E–deficient; CMTMR, 5-(and 6)-([{4-chloromethyl}benzoyl] amino) tetramethylrhodamine; HEV, high endothelial venule; oxLDL, oxidized low density lipoprotein; pLN, peripheral LN; Rag-1–/– mice, recombination activating gene 1–deficient mice; RBC, red blood cell; vDC, vascular DC; WD, Western Diet.


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