CD1 expression in human atherosclerosis. A potential mechanism for T cell activation by foam cells.
Atherosclerotic plaques are chronic inflammatory lesions composed of dysfunctional endothelium, smooth muscle cells, lipid-laden macrophages, and T lymphocytes. This study analyzed atherosclerotic tissue specimens for expression of CD1 molecules, a family of cell surface proteins that present lipid antigens to T cells, and examined the possibility that CD1+ lipid-laden macrophages might present antigen to T cells. Immunohistochemical studies using a panel of specific monoclonal antibodies demonstrated expression of each of the four previously characterized human CD1 proteins (CD1a, -b, -c, and -d) in atherosclerotic plaques. Expression of CD1 was not observed in normal arterial specimens and appeared to be restricted to the CD68+ lipid-laden foam cells of atherosclerotic lesions. CD1 molecules colocalized in areas of the arterial wall that also contained abundant T lymphocytes, suggesting potential interactions between CD1+ cells and plaque-infiltrating lymphocytes in situ. Using CD1-expressing foam cells derived from macrophages in vitro, we demonstrated the ability of such cells to present lipid antigens to CD1 restricted T cells. Given the abundant T cells, CD1+ macrophages, and lipid accumulation in atherosclerotic plaques, we propose a potential role for lipid antigen presentation by CD1 proteins in the generation of the inflammatory component of these lesions.
Melián
A
A
Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Geng
Y J
YJ
Sukhova
G K
GK
Libby
P
P
Porcelli
S A
SA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D018949:Antigens, CD1 / Q000096:biosynthesis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism*; D002642:Chick Embryo; D005434:Flow Cytometry; D005487:Foam Cells / Q000276:immunology / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D008055:Lipids / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D000097382:CD68 Molecule
D015703:Antigens, CD; D018949:Antigens, CD1; D015214:Antigens, Differentiation, Myelomonocytic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015847:Interleukin-4; D008055:Lipids; C067980:CD68 antigen, human; D000097382:CD68 Molecule