PMID- 32215844
OWN - NLM
STAT- MEDLINE
DCOM- 20211020
LR  - 20211203
IS  - 1557-1904 (Electronic)
IS  - 1557-1890 (Print)
IS  - 1557-1890 (Linking)
VI  - 15
IP  - 4
DP  - 2020 Dec
TI  - Delta(9)-Tetrahydrocannabinol (THC) Impairs CD8(+) T Cell-Mediated Activation of 
      Astrocytes.
PG  - 863-874
LID - 10.1007/s11481-020-09912-z [doi]
AB  - CD8(+) T cells can contribute to neuroinflammation by secretion of inflammatory 
      cytokines like interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha). 
      Astrocytes, a glial cell in the brain, can be stimulated by IFNgamma and TNFalpha to 
      secrete the inflammatory cytokines, monocyte chemotactic protein 1 (MCP-1), 
      interleukin 6 (IL-6), and interferon-gamma inducible protein 10 (IP-10). 
      Delta(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/IFNalpha- 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 IFNgamma, TNFalpha, and lysosomal-associated 
      membrane protein 1 (LAMP-1) expression. Recombinant TNFalpha and IFNgamma 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 IFNgamma and 
      degranulation responses were sensitive to THC-mediated ablation while TNFalpha was 
      not. Lastly, THC treatment reduced the IFNgamma-induced IP-10 response but had no 
      effect on TNFalpha-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.
FAU - Henriquez, Joseph E
AU  - Henriquez JE
AD  - Michigan State University, East Lansing, MI, USA.
AD  - Department of Pharmacology and Toxicology, East Lansing, MI, USA.
AD  - Institute for Integrative Toxicology, Michigan State University, 1129 Farm Lane, 
      Rm 165G, Food Safety and Toxicology Building, East Lansing, MI, 48824, USA.
FAU - Bach, Anthony P
AU  - Bach AP
AD  - Michigan State University, East Lansing, MI, USA.
AD  - Center for Research on Ingredient Safety, East Lansing, MI, USA.
FAU - Matos-Fernandez, Karina M
AU  - Matos-Fernandez KM
AD  - Michigan State University, East Lansing, MI, USA.
FAU - Crawford, Robert B
AU  - Crawford RB
AD  - Michigan State University, East Lansing, MI, USA.
AD  - Institute for Integrative Toxicology, Michigan State University, 1129 Farm Lane, 
      Rm 165G, Food Safety and Toxicology Building, East Lansing, MI, 48824, USA.
FAU - Kaminski, Norbert E
AU  - Kaminski NE
AD  - Michigan State University, East Lansing, MI, USA. kamins11@msu.edu.
AD  - Department of Pharmacology and Toxicology, East Lansing, MI, USA. 
      kamins11@msu.edu.
AD  - Institute for Integrative Toxicology, Michigan State University, 1129 Farm Lane, 
      Rm 165G, Food Safety and Toxicology Building, East Lansing, MI, 48824, USA. 
      kamins11@msu.edu.
AD  - Center for Research on Ingredient Safety, East Lansing, MI, USA. 
      kamins11@msu.edu.
LA  - eng
GR  - T32-ES007255/ILSI Health and Environmental Sciences Institute/International
GR  - T32 ES007255/ES/NIEHS NIH HHS/United States
GR  - R01 DA047180/DA/NIDA NIH HHS/United States
GR  - DA047180/DA/NIDA NIH HHS/United States
GR  - R25 ES025060/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200326
PL  - United States
TA  - J Neuroimmune Pharmacol
JT  - Journal of neuroimmune pharmacology : the official journal of the Society on 
      NeuroImmune Pharmacology
JID - 101256586
RN  - 0 (Cannabinoid Receptor Agonists)
RN  - 7J8897W37S (Dronabinol)
SB  - IM
MH  - Astrocytes/*drug effects/metabolism
MH  - CD8-Positive T-Lymphocytes/*drug effects/metabolism
MH  - Cannabinoid Receptor Agonists/*administration & dosage
MH  - Coculture Techniques
MH  - Dose-Response Relationship, Drug
MH  - Dronabinol/*administration & dosage
MH  - Humans
PMC - PMC7529688
MID - NIHMS1579656
OTO - NOTNLM
OT  - Astrocytes
OT  - CD8+ T cells
OT  - Inflammation
OT  - Delta9-Tetrahydrocannabinol
COIS- Declaration of Conflicting interests The Authors declare no conflicting 
      interests.
EDAT- 2020/03/28 06:00
MHDA- 2021/10/21 06:00
PMCR- 2021/12/01
CRDT- 2020/03/28 06:00
PHST- 2019/12/09 00:00 [received]
PHST- 2020/03/02 00:00 [accepted]
PHST- 2020/03/28 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2020/03/28 06:00 [entrez]
PHST- 2021/12/01 00:00 [pmc-release]
AID - 10.1007/s11481-020-09912-z [pii]
AID - 10.1007/s11481-020-09912-z [doi]
PST - ppublish
SO  - J Neuroimmune Pharmacol. 2020 Dec;15(4):863-874. doi: 10.1007/s11481-020-09912-z. 
      Epub 2020 Mar 26.