title: Modulatory effects of alveolar macrophages on CD4+ T-cell IL-5 responses correlate with IL-1beta, IL-6, and IL-12 production.
abstract: Increasing evidence suggests that the pattern of T-cell cytokine production can be modulated by antigen presenting cell (APC)-derived factors during the cell interactions. Recently, it has been shown that alveolar macrophages (AMs) from atopic asthmatics (AA) but not atopic nonasthmatics (AN) enhance interleukin (IL)-5 production by CD4+ T-cells. The present study compared AM production of IL-1beta, IL-6, and IL-12, as well as their associated functional capacity to influence IL-5 production by allergen-specific CD4+ T-cells in 10 AA, 10 AN, and nine nonatopic control subjects (C). AMs from AA showed a relatively high production of IL-1beta and IL-6 (p<0.05) and a relatively low secretion of IL-12 compared to C, whereas AMs from AN and C behaved similarly. This study confirmed previous findings that co-culture with AMs augments IL-5 production from allergen-stimulated CD4+ T-cells only in AA and not in nonasthmatics even if they are atopic. On the other hand, stimulation with allergen alone did not enhance IL-5 production by CD4+ T-cells in either AA nor AN. AM-induced changes in CD4+ T-cell IL-5 production upon allergen stimulation significantly correlated with their ability to produce IL-1beta (r=0.59, p<0.01), IL-6 (r=0.56, p<0.01), and inversely with IL-12 (r=-64, p=0.002) in all atopic subjects, and even more closely with the ratio of IL-12/IL-1beta (r=-0.75, p<0.001) and IL-12/IL-6 production (r=-0.81, p<0.001) in these subjects. These findings suggest that the role of alveolar macrophages from atopic asthmatics in enhancing interleukin-5 production by allergen-specific CD4+ T-cells is due, at least partly, to their aberrant production of interleukin-1beta, interleukin-6, and particularly of interleukin-12.
authors.affiliation: Dept of Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Tang
authors.forename: J M
authors.initials: JM
authors.lastname: Rolland
authors.forename: C
authors.initials: C
authors.lastname: Ward
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Bish
authors.forename: F
authors.initials: F
authors.lastname: Thien
authors.forename: E H
authors.initials: EH
authors.lastname: Walters
mesh_terms: D000328:Adult; D000368:Aged; D000485:Allergens; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012882:Skin Tests
chemical_list: D000485:Allergens; D015415:Biomarkers; D007375:Interleukin-1; D015848:Interleukin-5; D015850:Interleukin-6; D007378:Interleukins; D018664:Interleukin-12