Effects of Cigarette Smoke on Immune Response: Chronic Exposure to Cigarette Smoke Impairs Antigen-Mediated Signaling in T Cells and Depletes IP3-Sensitive Ca²⁺ Stores1

Abstract

Chronic exposure of mice and rats to cigarette smoke affects T-cell responsiveness that may account for the decreased T-cell proliferative and T-dependent antibody responses in humans and animals exposed to cigarette smoke. However, the mechanism by which cigarette smoke affects the T cell function is not clearly understood. Our laboratory has shown that chronic exposure of rats to nicotine inhibits the antibody-forming cell response, impairs the antigen-mediated signaling in T cells, and induces T cell anergy. To determine the mechanism of cigarette smoke-induced immunosuppression and to compare it with chronic nicotine exposure, rats were exposed to diluted, mainstream cigarette smoke for up to 30 months or to nicotine (1 mg/kg b.wt./24 h) via miniosmotic pumps for 4 weeks, and evaluated for immunological function in vivo and in vitro. This article presents evidence suggesting that T cells from long-term cigarette smoke-exposed rats exhibit decreased antigen-mediated proliferation and constitutive activation of protein tyrosine kinase and phospholipase C-γ1 activities. Moreover, spleen cells from smoke-exposed and nicotine-treated animals have depleted inositol-1,4,5-trisphosphate-sensitive Ca²⁺ stores and a decreased ability to raise intracellular Ca²⁺ levels in response to T cell antigen receptor ligation. These results suggest that chronic smoking causes T cell anergy by impairing the antigen receptor-mediated signal transduction pathways and depleting the inositol-1,4,5-trisphosphate-sensitive Ca²⁺ stores. Moreover, nicotine may account for or contribute to the immunosuppressive properties of cigarette smoke.