Alveolar macrophages from atopic asthmatics, but not atopic nonasthmatics, enhance interleukin-5 production by CD4+ T cells.
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-1alpha, IL-1beta, IL-6, or tumor necrosis factor-alpha differentially suppressed macrophage-enhanced IL-5 production (p < 0.05 for IL-1beta and IL-6) and expression of the activation marker CD25 (p < 0.05 for IL-1alpha 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.
Tang
C
C
Department of Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
Rolland
J M
JM
Li
X
X
Ward
C
C
Bish
R
R
Walters
E H
EH
D000328:Adult; D000485:Allergens; D001249:Asthma / Q000150:complications / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications* / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000485:Allergens; D007375:Interleukin-1; D015848:Interleukin-5; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha