title: Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells.
abstract: The capacity of airway eosinophils, potentially pertinent to allergic diseases of the upper and lower airways, to function as professional APCs, those specifically able to elicit responses from unprimed, Ag-naive CD4(+) T cells has been uncertain. We investigated whether airway eosinophils are capable of initiating naive T cell responses in vivo. Eosinophils, isolated free of other APCs from the spleens of IL-5 transgenic mice, following culture with GM-CSF expressed MHC class II and the costimulatory proteins, CD40, CD80, and CD86. Eosinophils, incubated with OVA Ag in vitro, were instilled intratracheally into wild-type recipient mice that adoptively received i.v. infusions of OVA Ag-specific CD4(+) T cells from OVA TCR transgenic mice. OVA-exposed eosinophils elicited activation (CD69 expression), proliferation (BrdU incorporation), and IL-4, but not IFN-gamma, cytokine production by OVA-specific CD4(+) T cells in paratracheal lymph nodes (LN). Exposure of eosinophils to lysosomotropic NH(4)Cl, which inhibits Ag processing, blocked each of these eosinophil-mediated activation responses of CD4(+) T cells. By three-color fluorescence microscopy, OVA Ag-loaded eosinophil APCs were physically interacting with naive OVA-specific CD4(+) T cells in paratracheal LN after eosinophil airway instillation. Thus, recruited luminal airway eosinophils are distinct allergic "inflammatory" professional APCs able to activate primary CD4(+) T cell responses in regional LNs.
authors.affiliation: Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Wang
authors.forename: Ionita
authors.initials: I
authors.lastname: Ghiran
authors.forename: Klaus
authors.initials: K
authors.lastname: Matthaei
authors.forename: Peter F
authors.initials: PF
authors.lastname: Weller
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007262:Infusions, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000485:Allergens; D015703:Antigens, CD; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D000643:Ammonium Chloride; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin