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Joong C. Huh^1,2, Deborah H. Strickland¹, Frode L. Jahnsen^1,3, Debra J. Turner¹, Jenny A. Thomas¹, Sylvia Napoli¹, Iriani Tobagus¹, Philip A. Stumbles¹, Peter D. Sly¹ and Patrick G. Holt¹

¹ 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
² Niigata University School of Medicine, Niigata 951-8510, Japan
³ Institute of Pathology, Rikshospitalet, Oslo 0027, Norway

Address correspondence to Patrick G. Holt, Division of Cell Biology, Telethon Institute for Child Health Research, P.O. Box 855, West Perth, WA 6872, Australia. Phone: 61-8-9489-7838; Fax: 61-8-9489-7707; E-mail: patrick{at}ichr.uwa.edu.au

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.

Key Words: dendritic cells • asthma • respiratory mucosa • T cells • activation

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