Research paperCannabidiol (CBD) induces functional Tregs in response to low-level T cell activation

•CBD induces CD25 and FOXP3 on CD4+ T cells in response to Us/o, S/o and s3/28 stimulation.•CBD is most effective in inducing CD4+CD25+FOXP3+ T cells in response to Us/o.•Us/o + CBD increased FOXP3 expression on CD4+ cells derived from FOXP3-GFP mice.•Us/o + CBD induced FOXP3 in pre-purified CD4+CD25− and CD4+CD25+ T cells.•Us/o + CBD-induced CD4+CD25+ T cells suppressed responder cell proliferation.

Many effects of the non-psychoactive cannabinoid, cannabidiol (CBD), have been described in immune responses induced by strong immunological stimuli. It has also been shown that CBD enhances IL-2 production in response to low-level T cell stimulation. Since IL-2, in combination with TGF-β1, are critical for Treg induction, we hypothesized that CBD would induce CD4+CD25+FOXP3+ Tregs in response to low-level stimulation. Low-level T cell stimulation conditions were established based on minimal CD25 expression in CD4+ cells using suboptimal PMA/Io (4 nM/0.05 μM, S/o), ultrasuboptimal PMA/Io (1 nM/0.0125 μM, Us/o) or soluble anti-CD3/28 (400-800 ng each, s3/28). CBD increased CD25+FOXP3+ cells from CD4+, CD4+CD25+, and CD4+CD25− T cells, as well as in CD4+ T cells derived from FOXP3-GFP mice. Most importantly, the Us/o + CBD-induced CD4+CD25+ Tregs robustly suppressed responder T cell proliferation, demonstrating that the mechanism by which CBD is immunosuppressive under low-level T cell stimulation involves induction of functional Tregs.