Organic dust from pig environment induces activation of human T cells

Abstract: Farmers suffer more frequently from inflammatory airway disorders than the population in general and a ongoing airway inflammation has been shown also in symptomfree healthy farmers. Exposure in a swine confinement building causes an intense airway inflammation with recruitment of inflammatory cells, predominately neutrophils, in healthy, previously, non-exposed subjects. In the present study exposure to organic dust from a swine confinement house has been used as a model to study lymphocyte reaction and activation. We found an increased number of lymphocytes in bronchoalveolar lavage (BAL) fluid following exposure in a swine house. It was, moreover, found that BAL T lymphocytes of previously non- exposed subjects were activated as the expression of the lymphocyte activation markers CD69, CD25 and HLA-DR increased following exposure. In vitro stimulation of whole blood with dust from swine confinement buildings also resulted in an increased expression of the activation markers CD69, CD25 and HLA-DR. The expression of the activation markers was dose and time dependent and occurred similar to phytohaemagglutinin (PHA) stimulated cells. It was demonstrated that phagocytic cells and mediators released by phagocytic cells were of importance for lymphocyte activation following exposure to dust. In phagocyte depleted whole blood cells, and in peripheral blood mononuclear cell (PBMC) fractions, the dust did not induce CD69 expression on T cells. Neither was IL- 12 nor IFN-gamma found in plasma from these cell fractions. However, whole blood stimulated with swine dust, and plasma obtained from stimulated whole blood i.e. conditioned plasma, induced T cell activation and generated high concentrations of M- 12 and IFN-gamma. Monocytes (CD 14+) rapidly produced IL- 12 and TFN-alpha after one hour of stimulation with the dust whereas Tand NK cells produced IFN-gamma only after a prolonged incubation (22 hours) with swine dust. The IFN-gamma production by NK cells and the CD69 expression on T cells were reduced after pre-incubation with antibodies blocking the IL12 receptor. In conclusion, we have shown that swine dust induces airway influx and activation of human bronchoalveolar lavage T cells in vivo and in vitro. T cell activiation occurs in a time and dose dependent manner in vitro. The mechanisms of the T cell activation involve stimulation of phagocytic: cells and production of cytokines such as TNF-alpha IL-12 and IFN-gamma. The results indicate a crucial role for IL- 12 in the stimulation of T cells.