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Journal of Neuroimmune Pharmacology

, Volume 10, Issue 2, pp 333–343 | Cite as

Exposure to Δ9-Tetrahydrocannabinol Impairs the Differentiation of Human Monocyte-derived Dendritic Cells and their Capacity for T cell Activation

  • Michael D. RothEmail author
  • Julie T. Castaneda
  • Sylvia M. Kiertscher
ORIGINAL ARTICLE

Abstract

The capacity for human monocytes to differentiate into antigen-presenting dendritic cells (DC) can be influenced by a number of immune modulating signals. Monocytes express intracellular cannabinoid type 1 (CB1) and 2 (CB2) receptors and we demonstrate that exposure to Δ9-tetrahydrocannabinol (THC) inhibits the forskolin-induced generation of cyclic adenosine monophosphate in a CB2-specific manner. In order to examine the potential impact of cannabinoids on the generation of monocyte-derived DC, monocytes were cultured in vitro with differentiation medium alone [containing granulocyte/macrophage-colony stimulating factor (GM-CSF) and Interleukin-4 (IL-4)] or in combination with THC. The presence of THC (0.25–1.0 μg/ml) altered key features of DC differentiation, producing a concentration-dependent decrease in surface expression of CD11c, HLA-DR and costimulatory molecules (CD40 and CD86), less effective antigen uptake, and signs of functional skewing with decreased production of IL-12 but normal levels of IL-10. When examined in a mixed leukocyte reaction, DC that had been generated in the presence of THC were poor T cell activators as evidenced by their inability to generate effector/memory T cells or to stimulate robust IFN-γ responses. Some of these effects were partially restored by exposure to exogenous IL-7 and bacterial superantigen (S. aureus Cowans strain). These studies demonstrate that human monocytes express functional cannabinoid receptors and suggest that exposure to THC can alter their differentiation into functional antigen presenting cells; an effect that may be counter-balanced by the presence of other immunoregulatory factors. The impact of cannabinoids on adaptive immune responses in individuals with frequent drug exposure remains to be determined.

Keywords

Δ9-tetrahydrocannabinol Cannabinoid receptor Monocyte Dendritic cell T cell activation Cytokines 

Notes

Acknowledgments

Research reported in this publication was supported by the National Institute on Drug Abuse, National Institutes of Health, under award numbers 5-R01-DA003018 and 1-R01-DA037102. JT Castaneda was supported by a Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research from the National Institute on Drug Abuse, National Institutes of Health, under award numbers 1 F31 DA036293. Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research (CFAR) Flow Cytometry Core Facility that is supported by National Institutes of Health awards CA-16042 and AI-28697, and by the JCCC, the UCLA AIDS Institute, and the David Geffen School of Medicine at UCLA.

Conflicts of Interest

The authors declare that they have no conflict of interest.

Statement of Human Rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Michael D. Roth
    • 1
    Email author
  • Julie T. Castaneda
    • 2
  • Sylvia M. Kiertscher
    • 1
  1. 1.Department of Medicine, Division of Pulmonary and Critical CareDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Department of Medicine, Interdepartmental Program in Molecular Toxicology and the Division of Pulmonary and Critical CareDavid Geffen School of Medicine at UCLALos AngelesUSA

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