Zhang S, Petro T M
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln 68583, USA.
Int J Immunopharmacol. 1996 Aug-Sep;18(8-9):467-78. doi: 10.1016/s0192-0561(96)00054-9.
T cells were exposed to various concentrations of nicotine or smokeless tobacco extract (STE) during in vitro immune responses in order to examine effects upon expression of T cell costimulatory counter-receptors, CD28 and CTLA-4, and cytokine production. Splenic mononuclear cells (SPM) were exposed to 1:10(2) to 1:10(3) dilutions of STE or 1-100 micrograms/ml nicotine during 48 and 72 h of stimulation with anti-CD3. Expression of CD28 and CTLA-4 was evaluated with flow cytometry and production and expression of IL-2, IL-4, IL-10 and IFN-gamma were evaluated using ELISA and RT-PCR. The data here indicate that the percentage of CD4+ T cells expressing CD28 declined while percentage and intensity of CTLA-4 expression increased with exposure to a 1:10(2) dilution of STE during the T cell response. Exposure to nicotine decreased the percentage of CD4+ T cells expressing both CD28 and CTLA-4 and decreased the intensity of CD28 expression. Responding T cells exposed to nicotine produced significantly less Th1 cytokines, IL-2 and IFN-gamma, but significantly more Th2 cytokines, IL-4 and IL-10. Cytokine specific mRNA expression was only slightly affected by the exposure to nicotine. Thus, exposure of T cells to physiological concentrations of STE or nicotine can alter the T cell expression of CD28 and CTLA-4, and the CD4 T cell cytokine expression pattern.
为了研究对T细胞共刺激反受体CD28和CTLA-4的表达以及细胞因子产生的影响，在体外免疫反应过程中，将T细胞暴露于不同浓度的尼古丁或无烟烟草提取物（STE）中。在用抗CD3刺激48和72小时期间，将脾单核细胞（SPM）暴露于1:10(2)至1:10(3)稀释的STE或1-100微克/毫升的尼古丁中。用流式细胞术评估CD28和CTLA-4的表达，并用ELISA和RT-PCR评估IL-2、IL-4、IL-10和IFN-γ的产生和表达。此处数据表明，在T细胞反应过程中，随着暴露于1:10(2)稀释的STE，表达CD28的CD4+ T细胞百分比下降，而CTLA-4表达的百分比和强度增加。暴露于尼古丁会降低表达CD28和CTLA-4的CD4+ T细胞百分比，并降低CD28表达的强度。暴露于尼古丁的反应性T细胞产生的Th1细胞因子IL-2和IFN-γ明显减少，但Th2细胞因子IL-4和IL-10明显增多。细胞因子特异性mRNA表达仅受到尼古丁暴露的轻微影响。因此，T细胞暴露于生理浓度的STE或尼古丁可改变T细胞CD28和CTLA-4的表达以及CD4 T细胞细胞因子表达模式。
