Immunomodulatory effects of cannabinoids in human T-lymphocytes

Anja Schinwald, Francesc Galban-Horcajo , Eva Malone, Paula Smith

Research output: Contribution to journalMeeting abstract

Abstract

Background: Circulating levels of endocannabinoids are elevated in obese and hyperglycaemic patients and may contribute to immune dysfunction in obesity and diabetes. Cannabinoids have been shown to evoke both pro- and anti-inflammatory responses, acting via CB1 and CB2 receptors on immune cells. In the present study we compared the responses of human T-cells to varying concentrations (0.1–1000nM) of endocannabinoids (anandamide and 2-arachidonoylglycerol, 2-AG), a phytocannabinoid (Δ9-tetrahydrocannabinol, Δ9-THC), and a synthetic CB2 receptor agonist (JWH-015). Methods: Lymphocytes were isolated from the peripheral blood of healthy male and female subjects (n = 12; aged 20-30 years), and cell surface expression of the T-cell activation marker CD69 was assessed on CD3+, CD4+ and CD8+ T-cells following 24 h cannabinoid treatment, using four-colour flow cytometry. In addition, lymphocyte CB1 and CB2 receptor expression was measured by real-time RT-PCR. The human Jurkat T-cell line was used to assess the effects of cannabinoids on T cell migration, to the chemokine CXCL12, in single-well Boyden chemotaxis chambers (n = 4-5). Results: Endocannabinoids did not significantly alter T-cell activation, however, Δ9-THC increased the proportion of CD3+ T-cells expressing CD69 (from 1±0 to 3.59±1.54; P = 0.09) at low concentrations (0.1nM), and decreased (from 1±0 to 0.39±0.22; P<0.05) at high concentrations (100nM). JWH-015 suppressed PMA-induced %CD69 expression at all concentrations tested (from 1±0 to between 0.28±0.21 and 0.66±0.00; P<0.05). There were no significant differences between CD4+ and CD8+ T-cell phenotypes. CD69 was not correlated with CB1 or CB2 receptor mRNA expression. Endocannabinoids did not affect T-cell migration to CXCL12, while Δ9-THC and JWH-015 reduced T-cell migration in a concentration-dependent manner (e.g. for Δ9-THC: 100±0% cell migration score for control versus 93±7% at 1nM; 46±8% at 10nM; 27±19% at 100nM; and 0±0% at 1000nM; P<0.01). Conclusions: These data reveal differences in the immunomodulatory effect of endo- versus synthetic and phyto-cannabinoids and concentration-dependent effects, with low Δ9-THC concentrations stimulating and high concentrations inhibiting T-cell activation. Studies using selective CB1 and CB2 receptor antagonists are warranted to confirm the receptor involved in mediating these responses.
Original languageEnglish
Article number034P
JournalpA2 Online
Volume7
Issue number4
Publication statusPublished - 2009

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