Am. J. Respir. Crit. Care Med., Volume 157, Number 4, April 1998, 1120-1126

Alveolar Macrophages from Atopic Asthmatics, But Not Atopic Nonasthmatics, Enhance Interleukin-5 Production by CD4+ T Cells

CHIBING TANG, JENNIFER M. ROLLAND, XUN LI, CHRISTOPHER WARD, ROS BISH, and E. HAYDN WALTERS

Respiratory Immunology Group, Department of Respiratory Medicine, Alfred Hospital, Melbourne, Victoria; and Department of Medicine and Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia

Recent studies have demonstrated that different antigen-presenting cell (APC)-related factors in the microenvironment of a T cell may determine its profile and quantity of cytokine expression and production. We have therefore examined the effects of alveolar macrophages and peripheral blood monocytes on interleukin (IL)-5 production by peripheral blood CD4+ T cells from atopic people with asthma (AA), atopic people without asthma (AN), and nonatopic normal subjects (N). In response to allergen stimulation, IL-5 production was significantly enhanced by the 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-stimulated 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 significantly amplified IL-5 production only in AA patients (p < 0.05 or 0.01). Furthermore, IL-5 production by CD4+ cells in alveolar macrophage cocultures, stimulated by allergen or mitogen, was higher than that in monocyte cocultures in AA patients (p < 0.05). Conversely, in AN and N subjects, the IL-5 values for alveolar macrophage cocultures were lower than those for peripheral blood monocytes. In blocking studies, antibodies against IL-1, IL-1, IL-6, or tumor necrosis factor- differentially suppressed macrophage-enhanced IL-5 production (p < 0.05 for IL-1 and IL-6) and expression of the activation marker CD25 (p < 0.05 for IL-1 and IL-6) by allergen-stimulated CD4+ cells in AA patients. These observations suggest that alveolar macrophages influence the quantity of IL-5 production by T cells in the airways and, as a consequence, the development of asthma in atopic individuals.

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