Characterization of cannabidiol-induced increases in CD25 and FOXP3 expression on CD4+ T cells (IRC11P.421)

Abstract

Abstract Cannabis sativa-derived cannabinoid compounds are being investigated as potential immunosuppressive agents and important drug candidates for immune related diseases. Our previous data demonstrated that under conditions of suboptimal T cell activation, cannabidiol (CBD) could increase interleukin-2 (IL-2) production. Initially this result was surprising given that cannabinoids are immunosuppressive, but IL-2 can also contribute to regulatory T cell (Treg) induction. We tested the hypothesis that part of the mechanism for immunosuppression by CBD is induction of a Treg population in response to suboptimal activation. Splenocytes were treated with CBD or vehicle (VH; 0.1% ethanol) for 30 minutes, then stimulated with low concentrations of PMA and ionomycin (Io). CBD induced IL-2, TGF-β, CD25 and FOXP3 on CD4+ T cells in response to 4 nM PMA/0.05 µM Io after an overnight stimulation. Further characterization of this effect demonstrated that CBD also induced CD25 and FOXP3 on CD4+ T cells after a 5-day incubation with 1 nM PMA/0.01 µM Io. Interestingly, while CBD robustly induced IL-2 after an overnight incubation with 4 nM PMA/0.05 µM Io, the IL-2 in the culture supernatant dropped by day 5. Overall, these data suggest that the mechanism by which CBD is immunosuppressive might involve induction of Tregs in response to suboptimal activation of T cells.