Figure 8.

Delta-9-tetrahydrocannabinol (Δ⁹-THC) administration inhibited PD-1 expression in intestinal T cells after SIV infection. Zebra plot shows significantly high expression of programmed death 1 (PD-1) by intestinal CD4⁺ T cells in a VEH/SIV rhesus macaque at 180 days post infection compared to preinfection time point (A,B). In contrast, PD1 expression in intestinal CD4⁺ T cells is significantly reduced in THC/SIV rhesus macaques at 14- and 180-days post-SIV infection compared to VEH/SIV rhesus macaques (C). Zebra plot shows PD-1 expression on intestinal CD8⁺ T cells of a VEH/SIV rhesus macaque at 180 days post-infection (D,E). Like CD4⁺ T cells, the percentage of PD-1 expressing CD8⁺ T cells out of total CD8⁺ T cells was also significantly reduced in THC/SIV rhesus macaques at 180 days post-SIV infection compared to VEH/SIV rhesus macaques (F). Open red circles- VEH/SIV, Open blue squares- THC/SIV. Horizontal red and blue lines with P-values denote comparisons between time points within the VEH/SIV and THC/SIV groups, respectively. Left black brackets with an asterisk indicate statistical significance (p = 0.0143) between the VEH/SIV and THC/SIV groups for a given time point. Connecting blue and red lines (C,F) denote mean values of the respective population in the THC/SIV and VEH/SIV groups, respectively. Flow cytometry analysis to determine the effect of Δ⁹-THC on PD-1 expression in intestinal CD4⁺ and CD8⁺ T cells of SIV-infected rhesus macaques was performed once with four individual animals as biological replicates per group. Flow cytometry data were analyzed using linear mixed models with immune-marker outcomes being dependent variables, and treatment status (VEH vs. Δ⁹-THC) and days since the start of treatment (0, 14, 120, 180) being independent variables with fixed effects. Differences between two time points were analyzed using the Mann-Whitney U-test employing the Prism v5 software (GraphPad software). A p-value of ≤0.05 was considered significant.