Background: Antigen-specific Th1 cells as well as Tc1 cells, induced by biolistic gene transfer using plasmid DNA encoding the model allergen b-galactosidase (bGal) under control of the fascin promoter (pFascin-bGal), inhibited the elicitation of systemic Th2 immune responses and suppressed IgE production in an experimental mouse model. Moreover, protective biolistic DNA vaccination with pFascin-bGal prevented Th2-mediated lung pathology (eosinophilia) in sensitized mice locally challenged with bGal protein, but led to the recruitment of Th1/Tc1 cells into the lung, associated with substantial neutrophilic infiltration and the induction of airway hyperresponsiveness (AHR). Objective: To analyze the modalities of AHR induction in mice biolistically vaccinated with pFascin-bGal. Methods: BALB/c mice were immunized with pFascin-bGal using the gene gun. Subsequently, mice were challenged by consecutive intranasal application of bGal protein. CD4+ and CD8+ T cells, respectively, were depleted before and during the provocation phase by intraperitoneal injection of anti-CD4 (GK1.5) or anti-CD8 (53.6.72) monoclonal antibodies. Neutrophilic granulocytes were depleted by treatment of animals with either anti-Gr-1 monoclonal antibody RB6-8C5 or monoclonal antibody NIMP-R14. One day after the last challenge airway reactivity was assessed by whole body plethysmography, bronchoalveolar lavage (BAL) was performed and the frequency of IFN-g-producing CD8+ effector T cells in the lung was determined. Results: Whereas neutrophilia in the lung of immunized and challenged mice was considerably alleviated by depletion of CD4+ T cells, AHR was not significantly affected, implicating that the elicitation of AHR by CD8+ T cells is dissociated from the activity of neutrophils. This notion was verified by elimination of neutrophils during the provocation phase, likewise leading to unaltered AHR. In contrast to CD8+ T cells, CD4+ T cells induced strong neutrophilic infiltration and AHR. Transfer experiments with CD4+ or CD8+ T cell, separated from the airways of vaccinated and challenged mice, will probably reveal details of the effector mechanisms of Th1 and Tc1 cells operative in the elicitation of airway inflammation. Conclusions: Robust type 1 immune responses, although highly effective in the counter-regulation of local Th2-mediated pathology, might as well trigger inflammatory reactions in the lung and provoke the induction of AHR.