title: T-lymphocytes and monocytes in atherogenesis.
abstract: Atherosclerosis is characterized as a chronic inflammatory-fibroproliferative disease of the vessel wall. The attachment of monocytes and T-lymphocytes to the injured endothelium followed by their migration into the intima is one of the first and most crucial steps in lesion development. The co-localization of CD4+ T-cells and macrophages in the lesion, the abundant expression of HLA Class II molecules and the co-stimulatory molecule CD40 and its ligand (CD40L) indicate a contribution of cell-mediated immunity to atherogenesis. Transgenic mouse models revealed that dependent on the model T- and B-cells may promote lesion progression, monocytes and macrophages are in contrast essential for the development of atherosclerotic lesions. Apart from the local process in the vessel wall, systemic signs of an inflammatory reaction are also associated with lesion development. Thus plasma levels of C-reactive protein and fibrinogen and the white blood cell count are positively correlated to the risk of cardiovascular disease. Recently, an inflammatory phenotype of circulating peripheral blood monocytes could be demonstrated as a specific cellular correlate to lipid and lipoprotein risk factors. Thus the pool size of LPS receptor (CD14)dim and Fc gamma IIIa receptor (CD16a)+ monocytes positively correlates to plasma cholesterol levels, to triglycerides levels and to the apolipoprotein E4 (apo E4) phenotype in contrast to a negative correlation to the high density lipoprotein (HDL) cholesterol concentration. This CD14dim CD16a+ monocytes are further characterized by a high expression of beta 1- and beta 2-integrins, suggesting a higher capacity for attachment at sites of inflammation. A proinflammatory cytokine pattern and an expansion of these cells in other inflammatory diseases are indicating that these cells promote the inflammatory process during atherogenesis. Surface expression of the activation antigen CD45RA on monocytes in correlation to plasma LDL cholesterol and Lp(a) levels further indicates an inflammatory reaction. Regarding the potential mechanisms of the phenotypic changes of peripheral blood monocytes, in a serum free in vitro differentiation model supplemented with M-CSF monocytes from probands which are homozygous for apo E4 showed a significantly higher increase of CD16a expression compared to apo E3/E3 cells indicating that a genetic polymorphism of a single apolipoprotein gene locus may affect monocyte differentiation. The further characterization of the cellular immunology of monocytes and T-lymphocytes in lesion development will provide new specific diagnostic and therapeutic targets in atherogenesis.
authors.affiliation: Institute for Clinical Chemistry and Laborary Medicine, University of Regensburg. gerd.schmitz@klink.uni-regensburg.de
authors.forename: G
authors.initials: G
authors.lastname: Schmitz
authors.forename: A S
authors.initials: AS
authors.lastname: Herr
authors.forename: G
authors.initials: G
authors.lastname: Rothe
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology*; D003324:Coronary Artery Disease / Q000276:immunology*; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D017539:Tunica Intima / Q000276:immunology