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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.

Huh JC, Strickland DH, Jahnsen FL, Turner DJ, Thomas JA, Napoli S, Tobagus I, Stumbles PA, Sly PD, Holt PG - J. Exp. Med. (2003)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

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AHR after exposure to aerosolized OVA. Sensitized animals (n = 6 per group; ○) together with naive controls (•) were exposed to aerosolized OVA, and 24 h later MCh challenge was performed. The top shows a left shift in the airway dose response curve to MCh contrasted with no change in parenchymal responsiveness (bottom). Differences between test and control groups in this experiment (and in Figs. 3–6) were analyzed by Student's t test. *, P < 0.01; **, P < 0.05.
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fig2: AHR after exposure to aerosolized OVA. Sensitized animals (n = 6 per group; ○) together with naive controls (•) were exposed to aerosolized OVA, and 24 h later MCh challenge was performed. The top shows a left shift in the airway dose response curve to MCh contrasted with no change in parenchymal responsiveness (bottom). Differences between test and control groups in this experiment (and in Figs. 3–6) were analyzed by Student's t test. *, P < 0.01; **, P < 0.05.

Mentions: Next, we performed lung function studies as shown in Fig. 2. Exposure of sensitized animals to a single OVA aerosol challenge induced hyperresponsiveness to MCh 24 h later, as demonstrated by the shift in the MCh dose response curve in Fig. 2 A. The technique used (19) provides independent measures of MCh responsiveness in the conducting airways (airway resistance in Fig. 2 A) versus peripheral lung tissues (tissue elastance in Fig. 2 B), and it is noteworthy that the development of MCh hyperresponsiveness was restricted to the airways. These findings, notably antigen aerosol–induced recruitment of T cells and eosinophils into airway tissues and accompanying expression of airways hyperresponsiveness (AHR), are hallmarks of the human asthmatic response to allergen challenge and indicate the general suitability of this system for modeling the human disease.


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.

Huh JC, Strickland DH, Jahnsen FL, Turner DJ, Thomas JA, Napoli S, Tobagus I, Stumbles PA, Sly PD, Holt PG - J. Exp. Med. (2003)

AHR after exposure to aerosolized OVA. Sensitized animals (n = 6 per group; ○) together with naive controls (•) were exposed to aerosolized OVA, and 24 h later MCh challenge was performed. The top shows a left shift in the airway dose response curve to MCh contrasted with no change in parenchymal responsiveness (bottom). Differences between test and control groups in this experiment (and in Figs. 3–6) were analyzed by Student's t test. *, P < 0.01; **, P < 0.05.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196086&req=5

fig2: AHR after exposure to aerosolized OVA. Sensitized animals (n = 6 per group; ○) together with naive controls (•) were exposed to aerosolized OVA, and 24 h later MCh challenge was performed. The top shows a left shift in the airway dose response curve to MCh contrasted with no change in parenchymal responsiveness (bottom). Differences between test and control groups in this experiment (and in Figs. 3–6) were analyzed by Student's t test. *, P < 0.01; **, P < 0.05.
Mentions: Next, we performed lung function studies as shown in Fig. 2. Exposure of sensitized animals to a single OVA aerosol challenge induced hyperresponsiveness to MCh 24 h later, as demonstrated by the shift in the MCh dose response curve in Fig. 2 A. The technique used (19) provides independent measures of MCh responsiveness in the conducting airways (airway resistance in Fig. 2 A) versus peripheral lung tissues (tissue elastance in Fig. 2 B), and it is noteworthy that the development of MCh hyperresponsiveness was restricted to the airways. These findings, notably antigen aerosol–induced recruitment of T cells and eosinophils into airway tissues and accompanying expression of airways hyperresponsiveness (AHR), are hallmarks of the human asthmatic response to allergen challenge and indicate the general suitability of this system for modeling the human disease.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus