Effects of Diesel Exhaust Particles on Antigen-Presenting Cells and Antigen-Specific Th Immunity in Mice

Abstract

Diesel exhaust particles (DEP) exacerbate antigen-related airway inflammation and hyperresponsiveness in mice; however, the mechanisms remain undefined. The present study characterized more precisely which pathways and cellular events of the allergic response are amplified by DEP in view of the maturation/activation/function of antigen-presenting cells (APC) and the antigen-specific Th response. We evaluated the effects of DEP on the phenotype and function of bone marrow-derived dendritic cells (BMDC) in vitro and on the expression pattern of APC-related molecules in the murine lung in the presence or absence of antigen in vivo. Also, we tested the effects of in vivo DEP co-exposure with antigen on the splenic antigen-specific Th response in the context of cytokine production. DEP significantly increased both allogeneic and antigen (ovalbumin: OVA)-specific syngeneic T-cell proliferation in vitro. In addition, an in vivo experiment showed that repetitive pulmonary exposure to DEP plus antigen (OVA) increased the numbers of MHC class II+cells and those expressing CD11c, DEC205 (DC markers), CD80, CD86 (co-stimulatory molecules), F4/80 (a macrophage marker), and CD19 (a B-cell differentiation antigen) in the lung as compared to that of others (vehicle, DEP, or OVA). Furthermore, an ex vivo assay system demonstrated that splenic mononuclear cells primed by DEP plus OVA produced a greater amount of interleukin (IL)-4, IL-5, and IL-13 after in vitro antigen stimulation compared to those primed by the other treatments. In conclusion, enhancement of allergic responses by DEP can be explained via two novel mechanisms, i.e., enhancement effects on APC including DC and on antigen-specific Th response, which culminate in the promotion of local and systemic dysregulated Th immunity.