TY - JOUR
T1 - CD1 expression in human atherosclerosis
T2 - A potential mechanism for T cell activation by foam cells
AU - Melián, Agustín
AU - Geng, Yong Jian
AU - Sukhova, Galina K.
AU - Libby, Peter
AU - Porcelli, Steven A.
PY - 1999/9
Y1 - 1999/9
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)65176-0
DO - 10.1016/S0002-9440(10)65176-0
M3 - Article
C2 - 10487835
AN - SCOPUS:0032887983
SN - 0002-9440
VL - 155
SP - 775
EP - 786
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -