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Published on: September 27, 2013
Delta 9-Tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells
Michael Yuan1, Sylvia M Kiertscher, Qingwen Cheng
1Division of Pulmonary and Critical Care Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1690, USA.
Insights
Delta 9-tetrahydrocannabinol (THC) modulates human T cell responses by suppressing proliferation and altering cytokine production. These effects are primarily mediated through the CB2 receptor pathway, impacting T helper 1/T helper 2 cell balance.
Area of Science:
- Immunology
- Pharmacology
Background:
- Human leukocytes possess cannabinoid (CB) receptors, indicating potential roles for endogenous ligands and Delta 9-tetrahydrocannabinol (THC) in immune modulation.
- Cannabinoids are known to interact with the immune system, but their specific effects on human T cell activation and cytokine profiles require further elucidation.
Purpose of the Study:
- To investigate the immunomodulatory effects of Delta 9-tetrahydrocannabinol (THC) on human T cells.
- To determine the role of cannabinoid receptors, specifically CB2, in mediating THC's effects on T cell activation and cytokine production.
Main Methods:
- Human T cells were stimulated with allogeneic dendritic cells in the presence or absence of varying concentrations of THC.
- Assessed T cell proliferation, interferon-gamma production, and T helper 1 (Th1)/T helper 2 (Th2) cytokine balance using intracellular cytokine staining and mRNA analysis.
- Utilized the CB2 receptor antagonist SR144528 to probe the receptor-dependent mechanisms.
Main Results:
- THC significantly suppressed T cell proliferation and inhibited interferon-gamma production.
- THC exposure shifted the Th1/Th2 cytokine balance towards Th2, decreasing Th1 cytokine mRNA and increasing Th2 cytokine mRNA.
- The CB2 receptor antagonist SR144528 reversed the majority of THC-induced immunomodulatory effects.
Conclusions:
- Cannabinoids, particularly THC, can regulate human T cell activation and Th1/Th2 cell balance.
- These immunomodulatory effects are predominantly mediated through a CB2 receptor-dependent pathway.
- Findings suggest a potential therapeutic role for cannabinoids in managing immune responses.
Abstract:
Human leukocytes express cannabinoid (CB) receptors, suggesting a role for both endogenous ligands and Delta 9-tetrahydrocannabinol (THC) as immune modulators. To evaluate this, human T cells were stimulated with allogeneic dendritic cells (DC) in the presence or absence of THC (0.625-5 microg/ml). THC suppressed T cell proliferation, inhibited the production of interferon-gamma and shifted the balance of T helper 1 (Th1)/T helper 2 (Th2) cytokines. Intracellular cytokine staining demonstrated that THC reduced both the percentage and mean fluorescence intensity of activated T cells capable of producing interferon-gamma, with variable effects on the number of T cells capable of producing interleukin-4. Exposure to THC also decreased steady-state levels of mRNA encoding for Th1 cytokines, while increasing mRNA levels for Th2 cytokines. The CB2 receptor antagonist, SR144528, abrogated the majority of these effects. We conclude that cannabinoids have the potential to regulate the activation and balance of human Th1/Th2 cells by a CB2 receptor-dependent pathway.
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