Lung dendritic cells express higher stress proteins on higher allergen dose exposure and contribute to allergen tolerance induction

Different doses of allergen lead to different T lymphocyte responses which partly explain the phenomenon of low or high dose tolerance. Dendritic cells (DC) are responsible for driving the T lymphocyte responses to a variety of exogenous stimuli, but the mechanisms are not completely understood. Elucidate the mechanisms of how DCs drive the differentiation of T lymphocytes in response to different doses of allergen. Groups of male BALB/c mice (n=4-5) were sensitized intraperitoneally with sham or different doses (low: 10 g, high: 1000 g) of Der P1 (house dust mite allergen). They were exposed daily to aerosolized Der p1 allergen for 7 consecutive days. Different concentrations of Der p1 solution were nebulized: sham, low dose (15 g/mL), or high dose (1500 g/mL). Bronchoalveolar lavage fluid (BALF) was obtained from the lungs. Levels of IL-12 in BALF were measured. Lung tissue sections were then stained to detect the expression of Hsp70 by lung DCs. Lung DCs exposed to a higher sensitizing doses of Der p1 allergen tend to express significantly higher levels of Hsp70 and secrete higher levels of IL-12 in BALF. There was a significant positive correlation between the levels of Hsp70 expression by lung DCs with IL-12 levels in BALF (r=0.581). Higher exposure doses of allergen puts lung DCs under stressed condition thereby induced high expression of 'stress proteins' which may explain the mechanism of DCs drive the T lymphocyte response.