Department of Microbiology & Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.
Toxicol In Vitro. 2013 Sep;27(6):1992-2004. doi: 10.1016/j.tiv.2013.06.015. Epub 2013 Jul 11.
Natural killer (NK) cells and T cells play essential roles in innate and adaptive immune responses in protecting against microbial infections and in tumor surveillance. Although evidence suggests that smoking causes immunosuppression, there is limited information whether the use of smokeless tobacco (ST) products affects immune responses. In this study, we assessed the effects of two preparations of cigarette smoke, ST extract and nicotine on T cell and NK cell responses using Toll-like receptor-ligand stimulated human peripheral blood mononuclear cells (PBMCs). The tobacco product preparations (TPPs) tested included whole smoke conditioned media (WS-CM), total particulate matter (TPM) and a ST product preparation in complete artificial saliva (ST/CAS). The PBMCs were stimulated with polyinosinic:polycytidylic acid (poly I:C) and lipopolysaccharide (LPS). A marked reduction of the expression of intracellular IFN-γ and TNF-α was evident in NK cells and T cells treated with WS-CM and TPM. Consistently, attenuation of ligand-induced secretion of cytokines (IL-1β, IL-10, IL-12 and TNF-α) from PBMCs treated with WS-CM and TPM were observed. While the treatment with TPPs did not alter the expression of the maturation marker CD69, WS-CM and TPM inhibited the cytolytic activity of human PBMCs. Suppression of perforin by WS-CM was also detected. Although interference from the vehicle confounded the interpretation of effects of ST/CAS, some effects were evident only at high concentrations. Nicotine treatment minimally impacted expression of cytokines and cytolytic activity. Data presented herein suggests that the function of NK cells and T cells is influenced by exposure to TPPs (based on equi-nicotine units) in the following order: WS-CM>TPM>ST/CAS. These findings are consistent with the hypothesis put forward by others that chronic smoking leads to immunosuppression, an effect that may contribute to increased microbial infections and cancer incidence among smokers.
自然杀伤 (NK) 细胞和 T 细胞在保护免受微生物感染和肿瘤监测方面在先天和适应性免疫反应中发挥着重要作用。尽管有证据表明吸烟会导致免疫抑制，但关于使用无烟烟草 (ST) 产品是否会影响免疫反应的信息有限。在这项研究中，我们使用 Toll 样受体配体刺激的人外周血单核细胞 (PBMC) 评估了两种香烟烟雾制剂、ST 提取物和尼古丁对 T 细胞和 NK 细胞反应的影响。测试的烟草产品制剂 (TPP) 包括全烟雾条件培养基 (WS-CM)、总颗粒物 (TPM) 和完全人工唾液中的 ST 产品制剂 (ST/CAS)。PBMC 用聚肌苷酸：聚胞苷酸 (poly I:C) 和脂多糖 (LPS) 刺激。用 WS-CM 和 TPM 处理的 NK 细胞和 T 细胞中，细胞内 IFN-γ 和 TNF-α 的表达明显减少。一致地，观察到用 WS-CM 和 TPM 处理的 PBMC 诱导的细胞因子 (IL-1β、IL-10、IL-12 和 TNF-α) 分泌减少。虽然 TPP 处理不会改变成熟标志物 CD69 的表达，但 WS-CM 和 TPM 抑制了人 PBMC 的细胞毒性活性。还检测到 WS-CM 抑制穿孔素。虽然载体的干扰使 ST/CAS 影响的解释复杂化，但仅在高浓度下才会出现一些影响。尼古丁处理对细胞因子的表达和细胞毒性活性的影响最小。本文提供的数据表明，NK 细胞和 T 细胞的功能受 TPPs（基于等效尼古丁单位）暴露的影响，其影响顺序为：WS-CM>TPM>ST/CAS。这些发现与其他人提出的慢性吸烟导致免疫抑制的假设一致，这种效应可能导致吸烟者中微生物感染和癌症发病率增加。
