title: GM-CSF increases the ability of cultured macrophages to support autologous CD4+ T-cell proliferation in response to Dermatophagoides pteronyssinus and PPD antigen.
abstract: Previous studies have demonstrated an infiltration of monocytes and increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the asthmatic lung. To study the possible effects of this cytokine upon the differentiation and function of these newly recruited monocytes, we have developed a model in which monocytes isolated from human peripheral blood were differentiated into macrophages in serum in the presence or absence of GM-CSF. After 7 days, the macrophages increased in size and granularity, had increased phagocytic activity, and expressed various adhesion molecules, CD14 and major histocompatibility complex (MHC) class II. The effects of GM-CSF on antigen presentation by cultured macrophages on the antigen-specific proliferative response of CD4+ T cells to Dermatophagoides pteronyssinus or purified protein derivative of tuberculin and the mitogen phytohaemagglutinin was determined. CD4+ T-cell proliferation was reduced when either antigen was presented by macrophages cultured in serum alone, compared with the values obtained with freshly isolated monocytes. However, CD4+ cell proliferation was comparable to that observed with monocytes when antigen was presented by macrophages which had been pre-cultured with 50 U/ml GM-CSF. CD4+ T-cell proliferation to phytohaemagglutinin was similar when all three populations were used as accessory cells. High numbers of macrophages partially suppressed CD4+ T-cell proliferation in response to antigen presented by monocytes, but there was no significant difference between macrophages cultured in the presence or absence of GM-CSF. This data suggests that GM-CSF directs monocyte differentiation into macrophages with an antigen-presenting, rather than a suppressive, phenotype. Elevated levels of GM-CSF in the asthmatic lung may therefore maintain recently recruited monocytes in an inflammatory and T-cell activating state.
authors.affiliation: Department of Allergy & Respiratory Medicine, Guy's Hospital, London, UK.
authors.forename: J J
authors.initials: JJ
authors.lastname: Caulfield
authors.forename: C M
authors.initials: CM
authors.lastname: Hawrylowicz
authors.forename: D M
authors.initials: DM
authors.lastname: Kemeny
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
mesh_terms: D017951:Antigen Presentation; D039741:Antigens, Dermatophagoides; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis; D011994:Recombinant Proteins; D014373:Tuberculin / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D011994:Recombinant Proteins; D014373:Tuberculin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor