Magnitude of stimulation dictates the cannabinoid-mediated differential T cell response to HIVgp120
Magnitude of stimulation dictates the cannabinoid-mediated differential T cell response to HIVgp120
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DOI：
10.1189/jlb.0212082
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发表时间：
2012-11-01
影响因子：
5.5
通讯作者：
Kaminski, Norbert E.
中科院分区：
文献类型：
--
作者：
Chen, Weimin;Kaplan, Barbara L. F.;Kaminski, Norbert E.
大约25%的免疫功能低下的艾滋病毒患者吸食大麻是因为它可能有治疗作用。这些研究的目的是验证大麻衍生的大麻素对HIV抗原特异性T细胞效应器功能具有免疫调节作用的假设。建立了诱导抗HIVgp120多克隆T细胞反应的代理小鼠模型。THC是一种大麻衍生的大麻素，可抑制或增强小鼠CD8(+)T细胞的增殖和gp120特异性的CTL反应，具体取决于干扰素-伽马反应的大小。为了确定大麻素不同地调节T细胞反应的分子机制，用P/I或抗CD3/CD28抗体进行刺激，并研究了另一种大麻来源的大麻素CBD。THC或CBD分别在最佳或次佳刺激条件下抑制或增强小鼠脾细胞产生干扰素-γ和IL-2。大麻素对NFAT和人PBMCs在P/I刺激下核转位产生细胞因子的影响也有相似的差异。然而，THC和CBD升高了细胞内的钙，无论P/I的刺激水平如何，这表明大麻素诱导的钙升高为次优刺激的T细胞提供了适当的激活信号，但在最佳刺激的T细胞中提供了由于钙过量而产生的无能信号。总体而言，这些数据显示了大麻素对HIV抗原特异性反应的不同调制，并确定了导致这种效应的可能机制。J.Leukoc。比奥尔。92：1093-1102；2012。
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 HIVgp120 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-gamma 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-gamma 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. J. Leukoc. Biol. 92: 1093-1102; 2012.