In situ expression of B7 and CD40 costimulatory molecules by normal human lung macrophages and epithelioid cells in tuberculoid granulomas

Normal alveolar macrophages (AM) are not efficient in inducing the prolifer ation of resting T lymphocytes, and, rather, tend to inhibit pulmonary immu ne responses. In contrast, epithelioid cells (EC), activated macrophages th at play an essential role in the course of granulomatous responses, appear to stimulate T cell proliferation efficiently. The inability of macrophages to deliver potent costimulatory signals through the B7/CD28 and CD40/CD40L pathways could explain their weak accessory cell activity. Using MoAbs and immunohistochemical techniques, however, we found that essentially all AM in normal human lung tissue expressed B7-1, B7-2 and CD40 molecules, and mo st of these cells were strongly positive. Pulmonary macrophages in other co mpartments also expressed these costimulatory molecules; no differences in expression were observed comparing macrophages from smokers and non-smokers . Most AM recovered by bronchoalveolar lavage from normal lung segments als o strongly expressed B7-1, B7-2 and CD40 molecules. In comparison, resting blood monocytes were B7-1(-) and only moderately positive for B7-2. Activat ion of monocytes with lipopolysaccharide (LPS) induced expression of these costimulatory molecules to levels similar to that of AM from the control su bjects. EC in granulomatous lesions also expressed easily detectable levels of B7-1, B7-2 and CD40. T lymphocytes within and surrounding the granuloma s expressed CD28, the counter-receptor for B7, and many of these T cells al so expressed B7-1 and B7-2. These findings suggest that both AM and EC can deliver costimulatory signals through B7-1, B7-2 and CD40 molecules, and in dicate that the impairment in accessory cell activity observed for normal A M cannot be attributed to the absence of expression of these costimulatory molecules.