ORIGINAL ARTICLE

Journal of Neuroimmune Pharmacology

, Volume 8, Issue 5, pp 1239-1250

First online:

Cannabinoids Inhibit T-cells via Cannabinoid Receptor 2 in an In Vitro Assay for Graft Rejection, the Mixed Lymphocyte Reaction

  • Rebecca Hartzell RobinsonAffiliated withCenter for Substance Abuse Research, Temple University School of MedicineDepartment of Microbiology and Immunology, Temple University School of Medicine
  • , Joseph J. MeisslerAffiliated withCenter for Substance Abuse Research, Temple University School of MedicineDepartment of Microbiology and Immunology, Temple University School of Medicine
  • , Jessica M. Breslow-DeckmanAffiliated withDepartment of Microbiology and Immunology, Thomas Jefferson University
  • , John GaughanAffiliated withBiostatistics Consulting Center, Temple University School of Medicine
  • , Martin W. AdlerAffiliated withCenter for Substance Abuse Research, Temple University School of MedicineDepartment of Pharmacology, Temple University School of Medicine
  • , Toby K. EisensteinAffiliated withCenter for Substance Abuse Research, Temple University School of MedicineDepartment of Microbiology and Immunology, Temple University School of Medicine Email author 

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Abstract

Cannabinoids are known to have anti-inflammatory and immunomodulatory properties. Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes. This study tested the capacity of Δ9-tetrahydrocannabinol (Δ9-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation. Both CB2-selective agonists and Δ9-THC significantly suppressed the MLR in a dose dependent fashion. The inhibition was via CB2, as suppression could be blocked by pretreatment with a CB2-selective antagonist, but not by a CB1 antagonist, and none of the compounds suppressed the MLR when splenocytes from CB2 deficient mice were used. The CB2 agonists were shown to act directly on T-cells, as exposure of CD3+ cells to these compounds completely inhibited their action in a reconstituted MLR. Further, the CB2-selective agonists completely inhibited proliferation of purified T-cells activated by anti-CD3 and anti-CD28 antibodies. T-cell function was decreased by the CB2 agonists, as an ELISA of MLR culture supernatants revealed IL-2 release was significantly decreased in the cannabinoid treated cells. Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients.

Keywords

Cannabinoids Cannabinoid receptor 2 Mixed lymphocyte reaction T-cells Immunosuppression