Open AccessΔ9-Tetrahydrocannabinol (THC) Impairs CD8+ T Cell-Mediated Activation of Astrocytes
Author(s) -
Joseph E. Henriquez,
Anthony Bach,
Karina M Matos-Fernandez,
R. J. Crawford,
Norbert E. Kaminski
Publication year - 2020
Publication title -
journal of neuroimmune pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.219
H-Index - 70
eISSN - 1557-1904
pISSN - 1557-1890
DOI - 10.1007/s11481-020-09912-z
Subject(s) - δ9 tetrahydrocannabinol , tetrahydrocannabinol , chemistry , pharmacology , microbiology and biotechnology , neuroscience , cannabinoid , biology , biochemistry , receptor
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 9 -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.