Published online before print September 22, 2005, doi: 10.1161/01.ATV.0000187470.31662.fe
© 2005 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
The Lamina Adventitia Is the Major Site of Immune Cell Accumulation in Standard Chow-Fed Apolipoprotein E–Deficient Mice
From the Institute for Vascular Medicine (M.P.W.M., N.J., R.G., S.N., B.K., A.J.R.H.), Institute of Laboratory Animal Science (B.G.), Institute for Medical Statistics, Computer Sciences and Documentation (R.V.), Friedrich Schiller University of Jena, Germany; and the Departments of Physiology and Biochemistry (C.D.F.), Queen’s University, Kingston, Ontario, Canada.
Correspondence to A.J.R. Habenicht, Friedrich Schiller University Jena, Institute for Vascular Medicine, Bachstr. 18, D-07743 Jena, Germany. E-mail andreas.habenicht{at}mti.uni-jena.de
Objective— Cells of adaptive immunity have been implicated in atherogenesis. Though substantial information is available on immune cells in atherosclerotic lesions of the lamina intima, cells in the lamina adventitia have received less attention.
Methods and Results— The composition of immune cells in the innominate artery and abdominal aorta was examined in young, adult, and old apolipoprotein (apo) E–/– and wild-type mice on standard mouse chow. In the innominate artery of apoE–/– mice, adventitial T cells increased at 32, 52, and 78 weeks exceeding those of the intima by 6-, 24-, and 85-fold. Single T cells dominated in young mice, later T/B cell clusters emerged, and lymphoid-like structures reminiscent of inflammatory follicles formed preferentially in the abdominal aorta of old mice. Follicles contained organized sets of immune response-regulating cells: Interdigitating dendritic cells, T cell effectors, proliferating B cells, and plasma cells. Adventitial T cell inflammation was associated with a marked increase in transcripts of the chemokine MIP-1
in the aorta but not in spleen or liver.
Conclusions— Adventitial lymphocyte infiltration and formation of inflammatory follicle-like structures in the abdominal aorta of old apoE–/– mice point to the adventitia as a site of local adaptive immune reactions during atherogenesis in hyperlipidemic mice.
Progression of atherosclerosis in apoE–/– mice is associated with a large increase in adventitial T cells, formation of T/B cell clusters, and of lymphoid-like follicles in the aged aorta. Thus, the lamina adventitia is a major location of adaptive immunity during atherogenesis in apoE–/– mice.
Key Words: adventitia • atherosclerosis • leukocytes • immune system • inflammation
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