Chronic cannabinoid administration increases CD8+ lymphocyte apoptosis during early Simian Immunodeficiency Virus infection in rhesus macaques.

Abstract

Δ9‐tetrahydrocannabinol (Δ9‐THC), the primary psychoactive component of marijuana, is used to ameliorate Acquired Immune Deficiency Syndrome associated wasting. Cannabinoid receptors are expressed in cells of the immune system, raising the possibility that chronic Δ9‐THC use may impact on immune function, potentially affecting progression of human immunodeficiency virus infection. We examined the effects of chronic Δ9‐THC administration (0.32mg/kg i.m., 2 X daily, starting 30 d pre‐infection) on the early changes in lymphocyte counts, subpopulations, apoptosis, and proliferation in young adult male rhesus macaques at day 30 post simian immunodeficiency virus (SIVmac251; 100 TCID50/ml, i.v.) infection. SIV+ animals had lower (40%) lymphocyte CD4+/CD8+ ratio, 3‐7‐fold higher CD8+Ki67 expression (proliferation marker), without significant changes in total lymphocyte count, or CD4+ and CD8+caspase 3 expression (apoptosis marker) than time‐matched SIV‐ controls. THC‐treated SIV+ animals showed similarly decreased CD4+/CD8+, increased CD8+Ki67 expression, but higher expression of caspase 3 in CD8+ lymphocytes than time‐matched THC‐treated SIV‐ controls. We speculate that though modest the Δ9‐THC‐induced increase in CD8+ apoptosis may accentuate the CD4+/CD8+ imbalance during later stages of SIV infection. Supported NIDA‐020419‐01A1