In recent years, atherosclerosis has come to be understood as an inflammatory disease, and several markers of inflammation such as C-reactive protein are indicators of risk for future heart disease (1).

Innate immunity involving pattern recognition receptors is known to occur in the atherosclerotic artery, and Dr. Hansson describes the mechanisms of action of scavenger and Toll-like receptors on macrophages in the atherosclerotic lesion. The significance of macrophages in the development of atherosclerosis has been demonstrated in mouse studies where atherosclerosis-susceptible ApoE knockout mice having a defect in the development of monocytes into macrophages had dramatically reduced atherosclerosis (2).

The adaptive immunity has also been implicated in atherosclerosis, as T cells cloned from human atherosclerotic lesions were found to react to oxidized LDL (3). CD4+ T cells (4) NKT cells (5) and disruption of TGF-beta regulation of T cells (6) have all been shown to increase atherosclerosis in mice.

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After viewing this presentation the participant will be able to discuss:

- Mechanisms of innate immunity in atherosclerosis involving macrophages and pattern recognition receptors
- Mechanisms of adaptive immunity in atherosclerosis involving T cells

1. Peter Libby, MD; Paul M. Ridker, MD; Attilio Maseri, MD.Inflammation and Atherosclerosis Circulation. 2002;105:1135.

2. JD Smith, E Trogan, M Ginsberg, C Grigaux, J Tian and M Miyata. Decreased Atherosclerosis in Mice Deficient in Both Macrophage Colony-Stimulating Factor (op) and Apolipoprotein EProceedings of the National Academy of Sciences, Vol 92, 8264-8268.

3. S Stemme, B Faber, J Holm, O Wiklund, JL Witztum and GK Hansson. T Lymphocytes from Human Atherosclerotic Plaques Recognize Oxidized Low Density LipoproteinProceedings of the National Academy of Sciences, Vol 92, 3893-3897.

4. Xinghua Zhou, MD, PhD; Antonino Nicoletti, PhD; Rima Elhage, PhD; Göran K. Hansson, MD, PhD.Transfer of CD4+ T Cells Aggravates Atherosclerosis in Immunodeficient Apolipoprotein E Knockout Mice Circulation. 2000;102:2919.

5. Emmanuel Tupin, Antonino Nicoletti, Rima Elhage, Mats Rudling, Hans-Gustaf Ljunggren, Göran K. Hansson, and Gabrielle Paulsson Berne.CD1d-dependent Activation of NKT Cells Aggravates AtherosclerosisJEM, Volume 199, Number 3, 417-422.

6. Anna-Karin L. Robertson, Mats Rudling, Xinghua Zhou, Leonid Gorelik, Richard A. Flavell and Göran K. HanssonDisruption of TGF-ß signaling in T cells accelerates atherosclerosis J. Clin. Invest. 112:1342-1350 (2003).