Interferon- α-mediated Activation of T Cells from Healthy and HIV-infected Individuals is Suppressed by Δ 9 -Tetrahydrocannabinol i.

HIV patients routinely use medicinal cannabinoids to treat neuropathic pain, anxiety, and HIV-associated wasting. However, Δ ⁹ -Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in cannabis, suppresses T cell function and secretion of interferons, both critically important in the anti-viral immune response. Interferon- α (IFN α), a key cytokine in T cell activation and peripheral control of HIV infection, can potentiate responsiveness to IL-7, a crucial homeostatic cytokine for peripheral T cell maintenance. . The objective of this investigation was to compare the response of T cells to stimulation by IFNα and IL-7 in T cells from healthy and HIV+ donors in the absence and presence of THC. T cells from healthy and HIV+ donors were stimulated in vitro with IFN α and IL-7 in the absence and presence of THC followed by measurements of signaling events through IFNAR, IFN α-induced expression of IL-7Rα, cognate signaling through IL-7R, and on IL-7-mediated T cell proliferation by flow cytometry and RT-qPCR. CD8⁺ T cells from HIV+ donors showed a diminished response to IFN α-induced pSTAT1 compared to CD8⁺ T cells from healthy donors while CD4⁺ T cells from HIV+ donors and healthy donors were comparable. Treatment with IFN α promoted IL-7R expression and potentiated IL-7-induced STAT5 phosphorylation to augment IL-7-mediated proliferation by T cells from healthy and HIV+ donors. Finally, HIV+ donors exhibited reduced sensitivity to THC-mediated suppression by IFN α and IL-7-mediated stimulation compared to healthy donors. These results further support THC as immune suppressive while identifying putatively beneficial aspects of cannabinoid-based therapies in HIV+ patients.