Δ 9 -Tetrahydrocannabinol (THC) Impairs CD8 + T Cell-Mediated Activation of Astrocytes

• Published in: Journal of neuroimmune pharmacology 2020-12, Vol.15 (4), p.863
• Main Authors: Henriquez, Joseph E, Bach, Anthony P, Matos-Fernandez, Karina M, Crawford, Robert B, Kaminski, Norbert E
• Format: Article
• Language: English
• Subjects: Astrocytes - drug effects; Astrocytes - metabolism; Cannabinoid Receptor Agonists - administration & dosage; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; Coculture Techniques; Dose-Response Relationship, Drug; Dronabinol - administration & dosage; Humans
• ISSN: 1557-1904

CD8 T cells can contribute to neuroinflammation by secretion of inflammatory cytokines like interferon γ (IFNγ) and tumor necrosis factor α (TNFα). Astrocytes, a glial cell in the brain, can be stimulated by IFNγ and TNFα to secrete the inflammatory cytokines, monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and interferon-γ inducible protein 10 (IP-10). Δ -Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in Cannabis sativa, possesses potent anti-inflammatory activity. The objective of this investigation was to assess the effects of THC treatment on CD8 T cell-mediated activation of astrocytes. CD3/CD28/IFNα- stimulated CD8 T cells were treated with vehicle (0.03% EtOH) or THC and cocultured with U251 astrocytes. IP-10 , MCP-1 , and IL-6 astrocytes were quantified by flow cytometry. LegendPlex™ was used to measure cytokine secretion by CD8 T cells and flow cytometry was employed to quantify IFNγ, TNFα, and lysosomal-associated membrane protein 1 (LAMP-1) expression. Recombinant TNFα and IFNγ were used to stimulate MCP-1, IP-10, IL-6 responses in U251 astrocytes, which were measured by flow cytometry. Treatment with THC reduced CD8 T cell-mediated induction of IP-10 and IL-6 responses in U251 astrocytes but had no effect on MCP-1. THC treatment differentially affected T cell effector functions such that IFNγ and degranulation responses were sensitive to THC-mediated ablation while TNFα was not. Lastly, THC treatment reduced the IFNγ-induced IP-10 response but had no effect on TNFα-induced MCP-1 response in U251 astrocytes. The results suggest that cannabinoid treatment can selectively reduce certain CD8 T cell responses that contribute to stimulation of astrocytes. Graphical Abstract Treatment with THC can abate CD8 T cell-dependent neuroinflammatory processes by inhibiting CD8 cell differentiation into effector cells, suppressing CD8 effector cell function, and reducing activation of astrocytes by CD8 T cell-derived inflammatory cytokines.