T-LYMPHOCYTES FROM HUMAN ATHEROSCLEROTIC PLAQUES RECOGNIZE OXIDIZED LOW-DENSITY-LIPOPROTEIN

Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characte rized by cholesterol deposition, fibrosis, and inflammation. The prese nce of activated T lymphocytes and macrophages and high expression of HLA class II molecules are indicative of a local immunologic activatio n in the atherosclerotic plaque, but the antigen(s) involved has not y et been identified. We established T-cell clones from human atheroscle rotic plaques using polyclonal mitogens as stimuli and exposed the clo nes to potential antigens in the presence of autologous monocytes as a ntigen-presenting cells. Four of the 27 CD4(+) clones responded to oxi dized low density lipoprotein (oxLDL) by proliferation and cytokine se cretion; this response was dependent on autologous antigen-presenting cells and restricted by HLA-DR. All clones that responded to oxLDL sec reted interferon gamma upon activation, but only one produced interleu kin 4, suggesting that the response to oxLDL results in immune activat ion and inflammation but may not be a strong stimulus to antibody prod uction, No significant response to oxLDL could be detected in CD4(+) T -cell clones derived from the peripheral blood of the same individuals . Together, the present data suggest that the inflammatory infiltrate in the atherosclerotic plaque is involved in a T-cell-dependent, autoi mmune response to oxLDL.