THC reduces proinflammatory T-cell accumulation in GVHD target organs. (A-C) PathHunter Chinese hamster ovary (CHO)-K1 CNR2 cells stably expressing the human CB2 receptor were used for signaling assays. Ratio of phosphorylated ERK (p-ERK) to total ERK (A), percentage of β-arrestin recruitment (B), and inhibition percentage of forskolin-induced cyclic adenosine monophosphate (cAMP) production (C) as a function of varying concentrations of JWH-133 and THC are depicted. The 50% effective concentration/50% inhibitory concentration and maximum effect values calculated from these curves are reported in Table 1. Symbols in panels A to C represent the mean from 3 to 6 determinations per assay. Lines drawn are the least squares best fit of the data to the nonlinear, 3-parameter log concentration-response relationship, where bottom (for p-ERK/ERK and β-arrestin) or top (for cAMP) values were constrained to 100. (D-G) Lethally irradiated Balb/c recipients received transplants of B6 BM and spleen cells (adjusted to yield an αβ T-cell dose of 0.85 × 10⁶ to 0.9 × 10⁶ cells). Animals were treated with THC (20 mg/kg; n = 9-14) or vehicle control (n = 10-15) for 21 days beginning on day 0. Balb/c mice receiving transplants of B6 BM alone served as controls (n = 7-10). The total numbers of CD4⁺ and CD8⁺ T cells in the colon and liver 21 days posttransplantation are shown in panel D. The absolute numbers of CD4⁺ or CD8⁺ T cells that produced IFN-γ (E) or GM-CSF (F) are depicted in these tissue sites. Total numbers of CD4⁺ Foxp3⁺ T cells in the colon or liver (G). Data are presented as the mean ± standard deviation and are cumulative results from 2 to 3 experiments. *P < .05, **P < .01, ***P < .001, ****P < .0001.