CD1 expression in human atherosclerosis. A potential mechanism for T cell activation by foam cells

Am J Pathol. 1999 Sep;155(3):775-86. doi: 10.1016/S0002-9440(10)65176-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / metabolism
  • Antigens, CD1 / biosynthesis*
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Arteriosclerosis / immunology
  • Arteriosclerosis / metabolism*
  • Chick Embryo
  • Flow Cytometry
  • Foam Cells / immunology
  • Foam Cells / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Inflammation / immunology
  • Interleukin-4 / pharmacology
  • Lipids / immunology
  • Lymphocyte Activation / immunology*
  • Microscopy, Fluorescence
  • Monocytes / drug effects
  • Monocytes / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Antigens, CD
  • Antigens, CD1
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Lipids
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor