DELTA-9-TETRAHYDROCANNABINOL DECREASES CYTOTOXIC LYMPHOCYTE-T ACTIVITY TO HERPES-SIMPLEX VIRUS TYPE-1-INFECTED CELLS

The purpose of this study was to examine the effect of DELTA(9)-tetrahydrocannabinol (DELTA(9)-THC), the major psychoactive component of marijuana, on T lymphocyte functional competence against herpes simplex virus Type 1 (HSV1) infection. Spleen cells from C3H/HeJ (H-2k) mice primed with HSV1 and exposed to DELTA(9)-THC were examined for anti-HSV1 cytolytic T lymphocyte (CTL) activity. Flow cytometry was used to determine whether DELTA(9)-THC altered T cytotoxic (Lyt-2+) and T helper (L3T4+) lymphocyte numbers or cell ratios. Nomarski optics microscopy was used to determine whether effector lymphocytes from drug-treated mice were able to bind to virally infected L929 (H-2k) target cells. Cytotoxicity assays demonstrated that CTL from mice exposed to DELTA(9)-THC were deficient in anti-HSV1 cytolytic activity. DELTA(9)-THC in vivo treatment had little effect on the number of T lymphocytes expressing the Lyt-2 or L3T4 antigens. Nomarski optics microscopy revealed that the CTL from the drug-treated mice were able to bind specifically to the HSV1-infected targets. However, DELTA(9)-THC in vivo exposure affected CTL cytoplasmic polarization toward the virus-infected target cell. CTL granule reorientation toward the effector cell-target cell interface following cell conjugation occurred at a lower frequency in co-cultures containing CTL from drug-treated mice. These results suggest that DELTA(9)-THC elicits dysfunction in CTL by altering effector cell-target cell postconjugation events.