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 atherectomy specimens. Lymphocytes and mononuclear leukocytes are also detectable in atherosclerotic surgical pathology specimens utilizing immunocytochemical techniques. Methods: In order to quantify the histological contribution of cytokine receptor-expressing immunocompetent cells to human coronary artery stenoses, 30 directional atherectomy catheter biopsy specimens (wet weight ≤10 mg) from 16 patients were snap frozen (-70°C) for quantitative immunocytochemical studies. Following computer-assisted squantification of total intimal nuclei per tissue section (mean 297±177; cell density 7±5/10⁴ μm²), monoclonal antibody cytochemistry was used to identify the percentage of these cells expressing antigenic clusters of differentiation (CD) charateristic of T-lymphocytes, B-lymphocytes and monocytes. Indentification of alpha (low affinity) and beta (intermediate affinity) interleukin-2 receptors on intimal cells was accomplished using a three-step streptavidin-biotin method. Results: A significant percentage of intimal cells were of lymphocytic (11±13%) or monocytic (12±14%) origin, with helper T-cells (9±12%) outnumbering both suppressor T-cells (2±4%) and B- lymphocytes (1±2%). Interleukin-2 receptor were noted on 9±12% of intimal cells, including cells with a vascular smooth muscle phenotype. Conclusions: These quantitative immunocytochemical data conclusively demonstrate that lymphocytes and monocytes account for over 20% of coronary plaque cells obtained by in-vivo atherectomy, and that helper (CD4) T-cells predominate over suppressor (CD8) T-cells and B-lymphocytes. Variable interleukin-2 receptor subtype expression occurs in mononuclear leukocytes infiltrating chronic human 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.