Effects of cigarette smoke on immune response: Chronic exposure to cigarette smoke impairs antigen-mediated signaling in T cells and depletes IP3-Sensitive Ca2+ stores

Chronic exposure of mice and rats to cigarette smoke affects T-cell respons iveness that may account for the decreased T-cell proliferative and T-depen dent antibody responses in humans and animals exposed to cigarette smoke. H owever, the mechanism by which cigarette smoke affects the T cell function is not clearly understood. Our laboratory has shown that chronic exposure o f rats to nicotine inhibits the antibody-forming cell response, impairs the antigen-mediated signaling in T cells, and induces T cell anergy. To deter mine the mechanism of cigarette smoke-induced immunosuppression and to comp are it with chronic nicotine exposure, rats were exposed to diluted, mainst ream 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 functi on in vivo and in vitro. This article presents evidence suggesting that T c ells from long-term cigarette smoke-exposed rats exhibit decreased antigen- mediated proliferation and constitutive activation of protein tyrosine kina se and phospholipase C-gamma 1 activities. Moreover, spleen cells from smok e-exposed and nicotine-treated animals have depleted inositol-1,4,5-trispho sphate-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 f or or contribute to the immunosuppressive properties of cigarette smoke.