Regulation of inflammatory t cell responses in the mouse lung

We have developed a mouse model of lung inflammation in response to aerosolized antigens. The degree of inflammation resulting from sensitization was evaluated by histological examination and by FACS analysis of leukocytes following enzymatic disassociation of the lung tissue. Animals that had been previously immunised by intra-peritoneal administration of lOOmg of ovalbumin (ova) adsorbed to aluminum hydroxide elicited a pronounced lung inflammatory response following intra-nasal (in) challenge by an aerosol of 2% ovalbumin (20 min. per day, for 8 days). The cell yields from the lungs of primed mice were 4.1x10and 17.0xlt> for animals m challenged with PBS and ovalbumin respectively. The lung inflammatory cells were predominantly eosinophils and neutrophils and were found to express CD1 Ib, heat stable antigen and la. The proportion of T cells present in the lungs of the animals did not increase during in exposure and the T cells present did not express IL-2 receptors or CD69. T cells isolated from lung tissue of mice immunised with ova failed to proliferate in response to ovalbumin when restimulated in vitro, but large amounts of IL-2 were present in the supernatants of such cultures. Removal of plastic adherent cells from the lung mononuclear cell fraction restored antigen induced proliferative responses. Adherent cells, predominantly macrophages, inhibited the ova response from sensitised spleen and the proliferation of the ova specific T cell hybrid DO. 11.10. Culture supemates from adherent cells inhibited the proliferation of the T cell hybrid, apparently by a Fas-mediated apoptosis. The induction of T cell apoptosis by lung macrophages forms an effective regulatory mechanism preventing chronic T cell activation in the lung mucosa.