Ozone Exposure Impairs Antigen-Specific Immunity but Activates IL-7-Induced Proliferation of CD4⁻CD8⁻ Thymocytes in Balb/c Mice

Abstract

It is well known that ozone (O₃), a potent reactive oxidant and air pollutant, induces respiratory inflammation and hyperresponsiveness upon inhalation. It was previously shown that O₃ exposure (0.6 ppm, 10 h/day for 15 days) not only results in local bronchial inflammation, but also affects the nervous system and thymocyte proliferation, and places mice under oxidative stress. In the present study, data showed that O₃ exposure could impair both the natural killer (NK) cell activity and the proliferation potential of spleen T cells to a specific antigen stimulus. Immunological function assays indicated that O₃ exposure attenuated the proliferation of spleen mononuclear cells induced by concanavalin A and decreased CD4⁺ and CD28⁺ lymphocyte subsets. However, supplementation with natural antioxidants protected mice from O₃-induced dysfunction of splenocyte proliferation. Meanwhile, O₃ exposure resulted in a decline of mitogen-induced IL-2 production in splenocytes. It was also found that O₃ exposure dramatically enhanced the proliferation of CD4⁻CD8⁻ thymocytes stimulated by recombinant mouse interleukin-7 (rmIL-7), which is usually observed during the mammal aging process. Taken together, data conclude that short-term repetitive O₃ exposure damages both innate and acquired immunity via altering the lymphocyte subset and cytokine profile, and via impact on thymocyte early development. O₃-induced oxidative damage is one of the key factors leading to immune dysfunction in this mouse model.

These studies were supported by the Japan Institute for the Control of Aging (JaICA97-00 Grant, W. He). The authors thank Drs. Wei Cui and Xiaoling Su (Peking Union Medical College Hospital) for their assistance on this project.

Notes

^a Statistical significance (p < .05) vs. control mice.

^a Statistical significance (p < .05) versus control mice.