Respiratory exposure to diesel exhaust particles decreases the spleen IgM response to a T cell-dependent antigen in female B6C3F1 mice.

We investigated the systemic immunotoxic potential of respiratory exposure to diesel exhaust particles (DEP) in this study. Female B6C3F1 mice (approximately 8 weeks old) were exposed to increasing concentrations of DEP intratracheally, 3 times every two weeks, and sacrificed 2 or 4 weeks after the first exposure. The systemic toxicity and immune status in mice were evaluated. Mice exposed to DEP (1 to 15 mg/kg) showed no significant changes in body, spleen, or liver weights. Lung weights were increased in the mice exposed to 15 mg/kg DEP for 2 or 4 weeks. Except for a decreased platelet count, no significant alterations occurred in hematological parameters following DEP exposure. The number of splenic anti-sheep red blood cell (sRBC) IgM antibody-forming cells (AFC) decreased following DEP exposure for 2 weeks. This effect was less severe following 4 weeks of exposure and was only evident in the high dose group. Exposure to DEP also resulted in a significant decrease in the absolute numbers and the percentages of total spleen cells for total, CD4(+), and CD8(+) T cells, while the numbers of B cells and total nucleated cells in spleen were not significantly changed. The proliferative response of splenocytes to the T-cell mitogen, concanavalin A (ConA), as well as their production of IL-2 and IFN-gamma, was decreased dose-dependently following exposure of mice to DEP for 2 weeks, whereas proliferation was not changed in response to anti-CD3 monoclonal antibody. In summary, short-term respiratory exposure of mice to DEP resulted in systemic immunosuppression with evidence of T cell-mediated and possibly macrophage-mediated mechanisms.