Nicotine Affects Host Immunity by Suppressing Th1-effector cells/IgG2a Production

OBJECTIVES: Epidemiological studies indicate that tobacco use may weaken host defenses and predispose individuals to oral cancer and periodontal diseases. Dendritic cells (DCs) are specialized cells that tailor host responses against cancer and pathogens by instructing the differentiation of Th1 cells, which promote the effector functions of natural killer cells, cytotoxic T cells and B-cell production of IgG2a in mice. Recently, we observed that nicotine, one of the major components of cigarette smoke, selectively suppresses the Th1-promoting capacity of DC in vitro. In this study, we examined the development of cellular and humoral immune responses to antigen challenge under the influence of nicotine in vivo.

METHODS: Wild-type BALB/c mice adoptively transferred with 2.5x106 ovalbumin (OVA)-specific T cells were exposed to saline (control) or nicotine (1mg/kg/day) using osmotic pumps. These mice were challenged with soluble OVA (2mg) plus bacterial antigen, lipopolysacharride (LPS, 50µg). Four days after immunization, cohorts of mice were sacrificed and lymphoid and splenic cells were isolated. The clonal expansion and the frequency of OVA-specific T cells producing IFN-gamma were measured by flow cytometry. The production of anti-OVA antibodies in blood sera samples collected eleven days after immunization was quantified by ELISA.

RESULTS: We found that the injection of soluble OVA plus LPS induced clonal expansion of adoptively transferred OVA-specific CD4+ T cells in lymphoid tissues of immunized control and nicotine-exposed mice. In control mice, this immunization promoted the generation of IFN-gamma secreting T cells and provided help for production of OVA-specific IgG2a. However, in nicotine-exposed mice, it significantly reduced both the frequency of IFN-gamma secreting T cells within OVA-specific proliferating cells as well as serum anti-OVA IgG2a.

CONCLUSIONS: Collectively, our in vitro and in vivo data suggests that nicotine weakens host immune defense mechanisms by affecting the development of DC-dependent Th1 cells. Phillip Morris USA and International.