title: Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions.
abstract: Our previous work revealed the presence of a great number of activated T lymphocytes in early human atherosclerotic lesions, and we were able to induce atherosclerosis in normocholesterolemic rabbits by immunization with Mycobacterium tuberculosis heat-shock protein (HSP) 65. We hypothesized this latter phenomenon to arise from cross-reactivity of mycobacterial HSP 65 with the endogenously expressed homologous 60-kd form of this stress protein. To study HSP 60 expression and the phenotype of intima infiltrating T lymphocytes relative to the T cell receptor (TCR) in human atherosclerotic lesions, specimens of aorta, carotid arteries, and internal mammary arteries and veins, as well as saphenous veins and vena cava from 27 subjects, aged 23 to 80 years, were examined using immunohistochemical and immunofluorescence techniques on serial frozen tissue sections. HSP 60 was detected on endothelium, smooth muscle cells, and/or mononuclear cells of all carotid and aortic specimens, whereas vessels of smaller diameter, serving as reference specimens for normal intima without atherosclerotic lesions and mononuclear infiltration, showed no detectable expression of this stress protein. Furthermore, although the majority of CD3+ cells within the mononuclear cell infiltrates of atherosclerotic lesions bear the alpha/beta TCR, a considerable portion also consisted of gamma/delta TCR+ cells. Thus, 9.7% of T cells in the transition zone between normal intima and fatty streaks carry the gamma/delta TCR, a proportion that decreases to 6.6% and 4.3% in fatty streaks and atherosclerotic plaques, respectively. We conclude that the intensity of HSP 60 expression correlates positively with the atherosclerotic severity and that most lymphocytes participating in atherogenesis bear the alpha/beta TCR, although gamma/delta TCR+ cells are also enriched in atherosclerotic lesions. Expression of HSP 60 by intimal cells, caused, eg, by hemodynamic shear forces, may be responsible for recruitment of HSP-sensitized T cells, thus leading to the induction of an initiating inflammatory process in atherosclerosis. Other risk factors, such as high serum cholesterol levels, contribute to the final outcome of the disease.
authors.affiliation: Institute for General and Experimental Pathology, University of Innsbruck Medical School, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Kleindienst
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Willeit
authors.forename: F R
authors.initials: FR
authors.lastname: Waldenberger
authors.forename: S
authors.initials: S
authors.lastname: Weimann
authors.forename: G
authors.initials: G
authors.lastname: Wick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001011:Aorta / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018834:Chaperonin 60; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000737:chemistry / Q000473:pathology; D017539:Tunica Intima / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D018834:Chaperonin 60; D006360:Heat-Shock Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta