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

Cell Immunol. 2017 Feb;312:25-34. doi: 10.1016/j.cellimm.2016.11.006. Epub 2016 Nov 9.


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 (4nM/0.05μM, S/o), ultrasuboptimal PMA/Io (1nM/0.0125μM, Us/o) or soluble anti-CD3/28 (400-800ng 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.

Keywords: CBD; CD4(+)CD25(+)FOXP3(+) Tregs; Immunosuppression.

MeSH terms

  • Animals
  • Cannabidiol / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Immunosuppression Therapy
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Tetradecanoylphorbol Acetate / immunology


  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Cannabidiol
  • Tetradecanoylphorbol Acetate