Macrophages, smooth muscle cells, endothelial cells, and T-cells express CD40 and CD40L in fatty streaks and more advanced human atherosclerotic lesions - Colocalization with epitopes of oxidized low-density lipoprotein, scavenger receptor, and CD16 (Fc gamma RIII)

CD40-CD40L receptor-ligand interaction plays a central role in antigen pres entation, immunological reactions, and in T-cell and macrophage activation. Since all these mechanisms are important for the pathogenesis of atheroscl erosis, we studied the expression profile of CD40-CD40L in different types of human atherosclerotic lesions using double immunostaining techniques wit h cell type-specific antibodies. Normal human intima did not contain CD40 o r CD40L immunoreactivity. From type-II lesions (fatty streaks) to advanced type-VI lesions (complicated plaques), colocalization of CD40 and CD40L was observed in T cells (CD3(+) cells), macrophages (CD68(+) cells), and smoot h muscle cells (HHF35(+) cells). No correlation was found between the lesio n type and CD40-CD40L expression. Positive lesions had dense infiltrations of macrophages and macrophage-derived foam cells together with T cells. The most intensive immunoreactivity for the CD40 receptor and its ligand CD40L was found in macrophage- and T-cell-rich pockets, where both cell types we re in close contact with each other. The majority of macrophages, and espec ially those of macrophage-derived foam cells, were positive for both CD40 a nd CD40L. A small subset of the lesion macrophage population (10-20%) consi sted of cells positive only for either CD40 or CD40L, suggesting the presen ce of a subpopulation of macrophages more active in inflammatory processes than in lipid uptake. Intimal smooth muscle cells in and around the macroph age-rich areas as well as some of the medial smooth muscle cells near the l esions stained positive for CD40 and CD40L. Moderate to faint expression of these proteins was also found in endothelium. In addition, CD40-CD40L immu noreactivity colocalized with epitopes characteristic of oxidized low-densi ty lipoprotein, scavenger receptor class A, and CD16 (Fc gamma RIII), thus suggesting the involvement of CD40-CD40L and these pathogenetic mediators i n foam cell formation, progression of atherosclerotic lesions, and differen tiation of immunologically active subsets of macrophages. These results sup port the hypothesis that CD40-CD40L interaction is Involved in atherogenesi s and that it might provide a target for future therapeutic interventions.