Costimulatory molecules in human atherosclerotic plaques: an indication of antigen specific T lymphocyte activation.
Atherosclerotic plaques contain inflammation, composed largely of macrophages and lymphocytes. A proportion of lymphocytes shows signs of activation, but the question arises whether they are activated in an antigen specific way. The expression of costimulatory molecules-receptors that provide accessory signals during antigen-specific activation is a prerequisite for such a condition. This aspect of inflammation in atherosclerotic lesions has not been investigated. Human arterial segments with diffuse intimal thickening, fatty streaks and atherosclerotic plaques were studied with immuno-single and double staining methods. Macrophages and T lymphocytes were stained with CD68 and CD3, respectively, and pan-B cell markers CD19 and CD22 were also used. Costimulatory molecules B7-1 and B7-2, together with their common ligand CD28, and CD27 with its ligand CD70, were stained with specific monoclonal antibodies. The results show that most T lymphocytes were CD27 positive and that only a subpopulation of these (5-15%) was positive also for B7-1, CD28 and CD70. Macrophages expressed B7-1, B7-2, CD28 and CD70, while macrophages positive for CD28 and CD70 have not been reported yet. The expression of costimulatory molecules was most pronounced in the superficial layers at the fibrous cap, but decreased towards the lipid core. This study shows, therefore, that atherosclerotic plaques provide costimulatory signals generally accepted as a prerequisite for adequate T cell stimulation. In addition, this study reveals that only approximately 5-15% of the lymphocytes appears actively involved in the inflammatory reaction.
de Boer
O J
OJ
Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
Hirsch
F
F
van der Wal
A C
AC
van der Loos
C M
CM
Das
P K
PK
Becker
A E
AE
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018941:Antigens, CD19 / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001158:Arteries / Q000166:cytology / Q000276:immunology / Q000473:pathology; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D053282:CD27 Ligand; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015815:Cell Adhesion Molecules; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000473:pathology; D000939:Epitopes; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000737:chemistry / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D051918:Sialic Acid Binding Ig-like Lectin 2; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D000097382:CD68 Molecule
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D015214:Antigens, Differentiation, Myelomonocytic; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D053282:CD27 Ligand; D018106:CD28 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D000939:Epitopes; D037102:Lectins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C497867:CD22 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C505771:CD70 protein, human; C497964:CD86 protein, human