title: Antigen-specific cytotoxic T lymphocytes target airway CD103+ and CD11b+ dendritic cells to suppress allergic inflammation.
abstract: Allergic airway inflammation is driven by the recognition of inhaled allergen by T helper type 2 (Th2) cells in the airway and lung. Allergen-specific cytotoxic T lymphocytes (CTLs) can strongly reduce airway inflammation, however, the mechanism of their inhibitory activity is not fully defined. We used mouse models to show that allergen-specific CTLs reduced early cytokine production by Th2 cells in lung, and their subsequent accumulation and production of interleukin (IL)-4 and IL-13. In addition, treatment with specific CTLs also increased the proportion of caspase(+) dendritic cells (DCs) in mediastinal lymph node (MLN), and decreased the numbers of CD103(+) and CD11b(+) DCs in the lung. This decrease required expression of the cytotoxic mediator perforin in CTLs and of the appropriate MHC-antigen ligand on DCs, suggesting that direct CTL-DC contact was necessary. Lastly, lung imaging experiments revealed that in airway-challenged mice XCR1-GFP(+) DCs, corresponding to the CD103(+) DC subset, and XCR1-GFP(-) CD11c(+) cells, which include CD11b(+) DCs and alveolar macrophages, both clustered in the areas surrounding the small airways and were closely associated with allergen-specific CTLs. Thus, allergen-specific CTLs reduce allergic airway inflammation by depleting CD103(+) and CD11b(+) DC populations in the lung, and may constitute a mechanism through which allergic immune responses are regulated.
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.|University of Otago, Wellington, New Zealand.
authors.forename: N J
authors.initials: NJ
authors.lastname: Daniels
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: E
authors.initials: E
authors.lastname: Hyde
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Lab for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Seo
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: K M
authors.initials: KM
authors.lastname: Price
authors.affiliation: Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan.|Department of Immunology, Faculty of Medicine, Kagawa University, Kita-gun, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hoshino
authors.affiliation: Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan.|Laboratory for Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University Suita, Osaka, Japan.|Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kaisho
authors.affiliation: Lab for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan.|PRESTO, Japan Science and Technology Agency, Saitama, Japan.|Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: F
authors.initials: F
authors.lastname: Ronchese
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology*; D020169:Caspases / Q000235:genetics / Q000276:immunology; D016923:Cell Death; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology*; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; D018793:Interleukin-13; D052899:Pore Forming Cytotoxic Proteins; D043562:Receptors, G-Protein-Coupled; C091671:XCR1 protein, human; C091367:alpha E integrins; C483886:perforin, mouse; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D010047:Ovalbumin; D020169:Caspases