抄録
The US Centers for Disease Control estimate that approximately 1.2 million US citizens are infected with HIV. Research shows the prevalence of cannabis use to be between 25 and 37% by HIV patients. Cannabinoids, including Δ9-tetrahydrocannabinol (THC), the major psychoactive constituent in cannabis, are well-established immune modulators. The impact of cannabis use by HIV patients on immune competence is poorly understood. The objective of the present study was to determine whether THC impairs Interferon alpha (IFNα) production by plasmacytoid dendritic cells (pDCs) and if so, the putative downstream effect on T cell function, including IL-7Rα expression. IFNα release is critical in the anti-viral host defense by exerting a broad spectrum of activity including promoting T cell responsiveness and expansion, in part, through up-regulation of IL-7Rα on T cells. Human pDCs from HIV- or HIV+ donors were strongly induced by CpG-ODN to secrete IFNα and suppressed by THC. Quantitative PCR confirmed cannabinoid receptor (CBR) 1 and 2 expression by pDC. THC treatment decreased the percentage of pDC expressing the critical SLAM receptor adaptor protein, EAT-2, providing insights into THC-mediated IFNα suppression. T cells demonstrated an elevation of surface IL-7Rα following IFNα treatment, which was significantly attenuated by THC. Interestingly, CD4+ and CD8+ T cells from HIV+ donors were more responsive to IFNα, as measured by IL7Rα up-regulation, than from HIV- donors. These studies show that THC suppressed pDC-derived IFNα release in HIV- and HIV+ donors, with impairment of IL-7Rα responsiveness to IL-7 stimulation.
