IMMUNOHISTOCHEMICAL CHARACTERIZATION OF IMMUNE CELL COMPOSITION AND CYTOKINE RECEPTOR EXPRESSION IN HUMAN CORONARY ATHERECTOMY TISSUE

Background: Prior histologic studies have examined smooth muscle cell, macrophage and thrombus constituents of atherosclerotic coronary athe rectomy specimens. Lymphocytes and mononuclear leukocytes are also det ectable in atherosclerotic surgical pathology specimens utilizing immu nocytochemical techniques. Methods: In order to quantify the histologi cal contribution of cytokine receptor-expressing immunocompetent cells to human coronary artery stenoses, 30 directional atherectomy cathete r biopsy specimens (wet weight less than or equal to 10 mg) from 16 pa tients were snap frozen (-70 degrees C) for quantitative immunocytoche mical studies. Following computer-assisted quantification of total int imal nuclei per tissue section (mean 297+/-177; cell density 7+/-5/10( 4) mu m(2)), monoclonal antibody cytochemistry was used to identify th e percentage of these cells expressing antigenic clusters of different iation (CD) characteristic of T-lymphocytes, B-lymphocytes and monocyt es. Identification of alpha (low affinity) and beta (intermediate affi nity) interleukin-2 receptors on intimal cells was accomplished using a three-step streptavidin-biotin method. Results: A significant percen tage of intimal cells were of lymphocytic (11+/-13%) or monocytic (12/-14%) origin, with helper T-cells (9+/-12%) outnumbering both suppres sor T-cells (2+/-4%) and B-lymphocytes (1+/-2%). lnterleukin-2 recepto rs were noted on 9+/-12% of intimal cells, including cells with a vasc ular smooth muscle phenotype. Conclusions: These quantitative immunocy tochemical data conclusively demonstrate that lymphocytes and monocyte s account for over 20% of coronary plaque cells obtained by in-vivo at herectomy, and that helper (CD4) T-cells predominate over suppressor ( CD8) T-cells and B-lymphocytes. Variable interleukin-2 receptor subtyp e expression occurs in mononuclear leukocytes infiltrating chronic hum an atheroma. By applying these techniques, the therapeutic effects of cytotoxic agents on selectively targeted cytokine receptor-expressing cells may now be evaluated in vivo in small human directional coronary atherectomy specimens.