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Research ArticleInflammation, Immunopharmacology, and Asthma

Interferon-α–Mediated Activation of T Cells from Healthy and HIV-Infected Individuals Is Suppressed by Δ9-Tetrahydrocannabinol

Joseph E. Henriquez, Michael D. Rizzo, Robert B. Crawford, Peter Gulick and Norbert E. Kaminski
Journal of Pharmacology and Experimental Therapeutics October 2018, 367 (1) 49-58; DOI: https://doi.org/10.1124/jpet.118.250308
Joseph E. Henriquez
Departments of Pharmacology and Toxicology (J.E.H., N.E.K.), Cell and Molecular Biology (M.D.R.), and Osteopathic Medicine (P.G.), and Institute for Integrative Toxicology (J.E.H., M.D.R., R.B.C., N.E.K.), Michigan State University, East Lansing, Michigan
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Michael D. Rizzo
Departments of Pharmacology and Toxicology (J.E.H., N.E.K.), Cell and Molecular Biology (M.D.R.), and Osteopathic Medicine (P.G.), and Institute for Integrative Toxicology (J.E.H., M.D.R., R.B.C., N.E.K.), Michigan State University, East Lansing, Michigan
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Robert B. Crawford
Departments of Pharmacology and Toxicology (J.E.H., N.E.K.), Cell and Molecular Biology (M.D.R.), and Osteopathic Medicine (P.G.), and Institute for Integrative Toxicology (J.E.H., M.D.R., R.B.C., N.E.K.), Michigan State University, East Lansing, Michigan
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Peter Gulick
Departments of Pharmacology and Toxicology (J.E.H., N.E.K.), Cell and Molecular Biology (M.D.R.), and Osteopathic Medicine (P.G.), and Institute for Integrative Toxicology (J.E.H., M.D.R., R.B.C., N.E.K.), Michigan State University, East Lansing, Michigan
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Norbert E. Kaminski
Departments of Pharmacology and Toxicology (J.E.H., N.E.K.), Cell and Molecular Biology (M.D.R.), and Osteopathic Medicine (P.G.), and Institute for Integrative Toxicology (J.E.H., M.D.R., R.B.C., N.E.K.), Michigan State University, East Lansing, Michigan
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Abstract

Patients with HIV routinely use medicinal cannabinoids to treat neuropathic pain, anxiety, and human immunodeficiency virus (HIV)–associated wasting. However, Δ9-tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in cannabis, suppresses T-cell function and secretion of interferons, both critically important in the antiviral immune response. Interferon-α (IFNα), a key cytokine in T-cell activation and peripheral control of HIV infection, can potentiate responsiveness to interleukin-7 (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. To compare T-cell responses between healthy and HIV+ donors signaling through IFNα receptor, IFNα-induced expression of IL-7α receptor (IL-7Rα), cognate signaling through IL-7R, and on IL-7–mediated T-cell proliferation were measured by flow cytometry and real-time quantitative polymerase chain reaction. CD8+ T cells from HIV+ donors showed a diminished response to IFNα-induced phosphorylated signal transducer and activator of transcription-1 activation compared with CD8+ T cells from healthy donors, whereas CD4+ T cells from HIV+ donors and healthy donors were comparable. Treatment with IFNα 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 IFNα- and IL-7–mediated stimulation compared with healthy donors. These results further support THC as being immune suppressive while identifying putatively beneficial aspects of cannabinoid-based therapies in HIV+ patients.

Footnotes

    • Received May 1, 2018.
    • Accepted June 28, 2018.
  • All funds for these studies were supplied through the National Institute on Drug Abuse Grants DA007908 and DA047180; and a National Institute of Environmental Health Sciences Training Grant T32-ES007255. No potential conflicts of interest relevant to this article are reported.

  • https://doi.org/10.1124/jpet.118.250308.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 367 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 367, Issue 1
1 Oct 2018
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Research ArticleInflammation, Immunopharmacology, and Asthma

THC Suppresses T-Cell Activation by IFNα and IL-7

Joseph E. Henriquez, Michael D. Rizzo, Robert B. Crawford, Peter Gulick and Norbert E. Kaminski
Journal of Pharmacology and Experimental Therapeutics October 1, 2018, 367 (1) 49-58; DOI: https://doi.org/10.1124/jpet.118.250308

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Research ArticleInflammation, Immunopharmacology, and Asthma

THC Suppresses T-Cell Activation by IFNα and IL-7

Joseph E. Henriquez, Michael D. Rizzo, Robert B. Crawford, Peter Gulick and Norbert E. Kaminski
Journal of Pharmacology and Experimental Therapeutics October 1, 2018, 367 (1) 49-58; DOI: https://doi.org/10.1124/jpet.118.250308
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