title: Bidirectional interactions between antigen-bearing respiratory tract dendritic cells (DCs) and T cells precede the late phase reaction in experimental asthma: DC activation occurs in the airway mucosa but not in the lung parenchyma.
abstract: The airway mucosal response to allergen in asthma involves influx of activated T helper type 2 cells and eosinophils, transient airflow obstruction, and airways hyperresponsiveness (AHR). The mechanism(s) underlying transient T cell activation during this inflammatory response is unclear. We present evidence that this response is regulated via bidirectional interactions between airway mucosal dendritic cells (AMDC) and T memory cells. After aerosol challenge, resident AMDC acquire antigen and rapidly mature into potent antigen-presenting cells (APCs) after cognate interactions with T memory cells. This process is restricted to dendritic cells (DCs) in the mucosae of the conducting airways, and is not seen in peripheral lung. Within 24 h, antigen-bearing mature DCs disappear from the airway wall, leaving in their wake activated interleukin 2R+ T cells and AHR. Antigen-bearing activated DCs appear in regional lymph nodes at 24 h, suggesting onward migration from the airway. Transient up-regulation of CD86 on AMDC accompanies this process, which can be reproduced by coculture of resting AMDC with T memory cells plus antigen. The APC activity of AMDC can be partially inhibited by anti-CD86, suggesting that CD86 may play an active role in this process and/or is a surrogate for other relevant costimulators. These findings provide a plausible model for local T cell activation at the lesional site in asthma, and for the transient nature of this inflammatory response.
authors.affiliation: Telethon Institute for Child Health Research and Centre for Child Health Research, Faculty of Medicine and Dentistry, The University of Western Australia, Perth, Western, Australia 6008.
authors.forename: Joong C
authors.initials: JC
authors.lastname: Huh
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Strickland
authors.forename: Frode L
authors.initials: FL
authors.lastname: Jahnsen
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Turner
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Thomas
authors.forename: Sylvia
authors.initials: S
authors.lastname: Napoli
authors.forename: Iriani
authors.initials: I
authors.lastname: Tobagus
authors.forename: Philip A
authors.initials: PA
authors.lastname: Stumbles
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001249:Asthma / Q000276:immunology*; D051940:B7-2 Antigen; D002450:Cell Communication; D003713:Dendritic Cells / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis; D009092:Mucous Membrane / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D012137:Respiratory System / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D010047:Ovalbumin