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Treatment of allergic lung disease mice with splenic CD8-alpha-positive dendritic cells down-regulates pulmonary Th2 responses and airway hyperresponsiveness

Treatment of allergic lung disease mice with splenic CD8-alpha-positive dendritic cells down-regulates pulmonary Th2 responses and airway hyperresponsiveness

FASEB Journal 18(4-5): Abst 769 8

As antigen-presenting cells, dendritic cells (DC) can either initiate and tolerize immune responses, depending on their phenotype -- freshly purified CD8-alpha-positive DC (CD8+DC), but not CD8-neg. DC, reportedly reduce the cytokine release and proliferative responses of lymphocytes to antigen challenge. Based on this evidence, we hypothesized that allergen-pulsed CD8+ DC might also down-regulate allergic lung disease (ALD) in mice. ALD was induced in BALB/c mice with two ip doses of OVA-alum (dy 0, 14), and three exposures to OVA aerosols. The mice displayed airway hyperresponsiveness (AHR), and Th2 responses, including eosinophilia and circulating OVA-specific IgE/IgG1. We purified CD8+DC (or CD8-neg. DC) from normal BAL/c mice using differential adherence and MACS, pulsed them with OVA, characterized them in vitro, then treated ALD mice intratracheally with varying numbers of these cells. In vitro, the CD8+DC expressed lower levels of CD80 and CD86 than did CD8-neg DC, but similar levels of CD40 and MHC-II. Perhaps not unexpectedly, the circulating OVA-specific IgG1 and IgE levels of the ALD mice were not markedly reduced 1-2 weeks following the splenic CD8+DC treatments, but the BAL levels of IL-5, IL-9, and IL-13 were remarkably depressed, and the BAL eosinophilia was reduced by 35-45%, relative to saline or CD8-neg DC-treated animals. Neither IFN-gamma nor IL-12 responses were detected in the airways of the treated animals, but there was a very marked augmentation of the OVA-specific IgA response. The AHR of the CD8+ DC-treated, but not CD8-neg DC-treated, mice was reduced dramatically; in some experiments as few as 10e4 CD8+ DC abrogated AHR to methacholine. (supported by the Saskatchewan Lung Association).

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