: Hartwig, C.; Mazzega, M.; Constabel, H.; Krishnaswamy, J.K.; Gessner, J.E.; Braun, A.; Tschernig, T.; Behrens, G.M.N.

Abstract
During asthma, lung DC capture and process antigens to initiate and maintain allergic Th2 cell responses to inhaled allergens. The aim of the study was to investigate whether allergen-specific IgG, generated during sensitization, can potentiate the acute airway inflammation through Fc gamma receptor (Fc gamma R)-mediated antigen uptake and enhance antigen presentation resulting in augmented T-cell proliferation. We examined the impact of antigen presentation and T-cell stimulation on allergic airway hyperresponsiveness and inflammation using transgenic and gene-deficient mice. Both airway inflammation and eosinophilia in bronchoalveolar lavage fluid were markedly reduced in sensitized and challenged Fc gamma R-deficient mice. Lung DC of WT, but not Fc gamma R-deficient mice, induced increased antigen-specific CD4(+) T-cell proliferation when pulsed with anti-OVA IgG immune complexes. Intranasal application of anti-OVA IgG immune complexes resulted in enhanced airwayinflammation, eosinophilia and Th2 cytokine release, mediated through enhanced antigen-specific T-cell proliferation in vivo. Finally, antigen-specific IgG in the serum of sensitized mice led to a significant increase of antigen-specific CD4(+) T-cell proliferation induced by WT, but not Fc gamma R-deficient, lung DC. We conclude that Fc gamma R-mediated enhanced antigen presentation and T-cell stimulation by lung DC has a significant impact on inflammatory responses following allergen challenge in asthma.