Cellular Basis of the Role of Diesel Exhaust Particles in Inducing Th2-Dominant Response

Abstract

There is growing evidence that diesel exhaust particles (DEP) can induce allergic diseases with increased IgE production and preferential activation of Th2 cells. To clarify the cellular basis of the role of DEP in the induction of Th2-dominant responses, we examined the effects of DEP on the cytokine production by T cells stimulated with anti-CD3/CD28 Ab and on that by monocyte-derived dendritic cells (MoDCs) stimulated with CD40L and/or IFN-γ. We examined IFN-γ, IL-4, IL-5, IL-8, and IL-10 produced by T cells and TNF-α, IL-1β, IL-10, and IL-12 produced by MoDCs using real-time PCR analysis or by ELISA. To highlight the effects of DEP, we compared the effects of DEP with those of dexamethasone (DEX) and cyclosporin A (CyA). DEP significantly suppressed IFN-γ mRNA expression and protein production, while it did not affect IL-4 or IL-5 mRNA expression or protein production. The suppressive effect on IFN-γ mRNA expression was more potent than that of DEX and comparable at 30 μg/ml with 10−7 M CyA. The suppressive effect on IFN-γ production was also more potent than that of either DEX or CyA. DEP suppressed IL-12p40 and IL-12p35 mRNA expression and IL-12p40 and IL-12p70 production by MoDCs, while it augmented IL-1β mRNA expression. Finally, by using a thiol antioxidant, N-acetyl cysteine, we found that the suppression of IFN-γ production by DEP-treated T cells was mediated by oxidative stress. These data revealed a unique characteristic of DEP, namely that they induce a Th2 cytokine milieu in both T cells and dendritic cells.

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*

“…Nasal challenge with diesel exhaust particles induces alterations in cytokine responses and an increase in IgE production (663). Diesel exhaust particles can induce allergic diseases with an increased IgE production and a preferential activation of Th2 cells (664)(665)(666). They may also act as an adjuvant of pollen allergens (667).…”

Diesel Exhaust Particles Stimulate Adaptive Immunity by Acting on Pulmonary Dendritic Cells

“…One could therefore speculate that DEP exposure has an impact on several aspects of the DC biology. Indeed, in vitro data demonstrated that DEP exposure induces DC maturation (10,11) via epithelial cell-derived mediators (12,13) and that DEP-exposed DCs induce a Th2 polarization (10,(13)(14)(15).…”

Activation of Pulmonary Dendritic Cells and Th2-Type Inflammatory Responses on Instillation of Engineered, Environmental Diesel Emission Source or Ambient Air Pollutant Particles in vivo

“…Studies exploring the role of DC activation and allergic risk in asthma development have focused on the adjuvant potential of PM to induce allergic sensitization to a coadministered antigen-like ovalbumin (OVA) or house dust mite [6,12,18,[28][29][30][31][32] . Often high and repeated doses of PM exposure are used that also induce tissue damage and general airway inflammation.…”