ALVEOLAR MACROPHAGES FROM ATOPIC ASTHMATICS, BUT NOT ATOPIC NONASTHMATICS, ENHANCE INTERLEUKIN-5 PRODUCTION BY CD4-CELLS( T)

Recent studies have demonstrated that different antigen-presenting cel l (APC)-related factors in the microenvironment of a T cell may determ ine its profile and quantity of cytokine expression and production. We have therefore examined the effects of alveolar macrophages and perip heral blood monocytes on interleukin (IL)-5 production by peripheral b lood CD4+ T cells from atopic people with asthma (AA), atopic people w ithout asthma (AN), and nonatopic normal subjects (N). In response to allergen stimulation, IL-5 production was significantly enhanced by th e addition of monocytes to CD4+ cell cultures in AA and AN patients (p < 0.05 and 0.01, respectively), but not in N subjects. In mitogen-sti mulated CD4+ cell plus monocyte cocultures, there was a small increase in IL-5 production in all three groups (p < 0.05 for AN). In contrast , the addition of alveolar macrophages to parallel cultures significan tly amplified IL-5 production only in AA patients (p < 0.05 or 0.01). Furthermore, IL-5 production by CD4+ cells in alveolar macrophage cocu ltures, stimulated by allergen or mitogen, was higher than that in mon ocyte cocultures in AA patients (p < 0.05). Conversely, in AN and N su bjects, the IL-5 values for alveolar macrophage cocultures were lower than those for peripheral blood monocytes. In blocking studies, antibo dies against IL-1 alpha, IL-1 beta, IL-6, or tumor necrosis factor-a d ifferentially suppressed macrophage-enhanced IL-5 production (p < 0.05 for IL-1 beta and IL-6) and expression of the activation marker CD25 (p < 0.05 for IL-1 alpha and IL-6) by allergen-stimulated CD4+ cells i n AA patients. These observations suggest that alveolar macrophages in fluence the quantity of IL-5 production by T cells in the airways and, as a consequence, the development of asthma in atopic individuals.