Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
J Leukoc Biol. 2012 Nov;92(5):1093-102. doi: 10.1189/jlb.0212082. Epub 2012 Aug 16.
Approximately 25% of immunocompromised HIV patients smoke marijuana for its putative therapeutic benefit. The goal of these studies was to test the hypothesis that marijuana-derived cannabinoids have immunomodulatory effects on HIV antigen-specific T cell effector function. A surrogate mouse model to induce polyclonal T cell responses against HIV(gp120) was established. THC, a marijuana-derived cannabinoid, suppressed or enhanced mouse CD8(+) T cell proliferation and the gp120-specific CTL response depending on the magnitude of the IFN-γ response. To determine the molecular mechanisms by which cannabinoids differentially modulate T cell responses, P/I or anti-CD3/CD28 antibodies were used for stimulation, and another marijuana-derived cannabinoid, CBD, was also investigated. THC or CBD suppressed or enhanced IFN-γ and IL-2 production by mouse splenocytes under optimal or suboptimal stimulation, respectively. Similar differential effects of cannabinoids on cytokine production were also observed on nuclear translocation of NFAT and with human PBMCs in response to P/I stimulation. However, THC and CBD elevated intracellular calcium, regardless of the stimulation level with P/I, suggesting that the cannabinoid-induced calcium increase provides an appropriate signal for activation in suboptimally stimulated T cells but an anergic-like signal as a result of excessive calcium in optimally stimulated T cells. Overall, these data demonstrate differential modulation by cannabinoids of a HIV antigen-specific response and identify a possible mechanism responsible for this effect.
大约 25%免疫功能低下的 HIV 患者吸烟大麻，因为它具有潜在的治疗益处。这些研究的目的是检验大麻衍生的大麻素对 HIV 抗原特异性 T 细胞效应功能是否具有免疫调节作用的假设。建立了一种用于诱导针对 HIV（gp120）的多克隆 T 细胞反应的替代小鼠模型。大麻衍生的大麻素 THC 取决于 IFN-γ 反应的幅度，抑制或增强了小鼠 CD8(+) T 细胞的增殖和 gp120 特异性 CTL 反应。为了确定大麻素差异调节 T 细胞反应的分子机制，使用 P/I 或抗-CD3/CD28 抗体进行刺激，并研究了另一种大麻衍生的大麻素 CBD。THC 或 CBD 分别在最佳或次优刺激下抑制或增强了小鼠脾细胞 IFN-γ 和 IL-2 的产生。在对 P/I 刺激的反应中，在核易位的 NFAT 和人类 PBMC 中也观察到了大麻素对细胞因子产生的类似差异效应。然而，无论用 P/I 进行刺激的水平如何，THC 和 CBD 都会增加细胞内钙，这表明大麻素诱导的钙增加为在次优刺激的 T 细胞中提供了适当的激活信号，但在最佳刺激的 T 细胞中由于钙过多而提供了一种类似无反应的信号。总的来说，这些数据表明大麻素对 HIV 抗原特异性反应具有差异调节作用，并确定了导致这种效应的可能机制。
