title: Human alveolar macrophages present antigen ineffectively due to defective expression of B7 costimulatory cell surface molecules.
abstract: Alveolar macrophages, resident phagocytic cells in the lung that derive from peripheral blood monocytes, are paradoxically ineffective in presenting antigen to T cells. We found that antigen presentation by alveolar macrophages could be restored by the addition of anti-CD28 mAb to cultures of T cells and macrophages, indicating that costimulation by alveolar macrophages via the CD28 pathway was defective. In addition, we found that alveolar macrophages activated with IFN-gamma failed to express B7-1 or B7-2 antigens, which normally ligate CD28 on T cells and provide a costimulatory signal required for the activation of T cells. These observations are the first to demonstrate the inability of a "professional" antigen-presenting cell type to effectively express the costimulatory molecules B7-1 and B7-2. Inasmuch as immune reactions within the lung are inevitably associated with inflammatory injury to pulmonary tissue, these observations suggest that reduced expression of B7-1 and B7-2 by alveolar macrophages may be advantageous, as a critical mechanism involved in the induction of peripheral tolerance to the abundance of antigens to which mucosal tissues are continuously exposed.
authors.affiliation: Division of Allergy, Immunology, and Respiratory Medicine, Stanford University, Lucile Salter Packard Children's Hospital, California 94305-5119.
authors.forename: C J
authors.initials: CJ
authors.lastname: Chelen
authors.forename: Y
authors.initials: Y
authors.lastname: Fang
authors.forename: G J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: H
authors.initials: H
authors.lastname: Secrist
authors.forename: J D
authors.initials: JD
authors.lastname: Marshall
authors.forename: P T
authors.initials: PT
authors.lastname: Hwang
authors.forename: L R
authors.initials: LR
authors.lastname: Frankel
authors.forename: R H
authors.initials: RH
authors.lastname: DeKruyff
authors.forename: D T
authors.initials: DT
authors.lastname: Umetsu
mesh_terms: D000328:Adult; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D018664:Interleukin-12