DELTA(9)-TETRAHYDROCANNABINOL SELECTIVELY INHIBITS MACROPHAGE COSTIMULATORY ACTIVITY AND DOWN-REGULATES HEAT-STABLE ANTIGEN EXPRESSION

Delta(9)-Tetrahydrocannabinol (THC) exposure inhibits numerous immunol ogic functions of macrophages. The ability of THC-exposed macrophages to provide costimulatory signals to helper T cell hybridomas was inves tigated by induction of interleukin-2 secretion by T cells in response to immobilized monoclonal anti-CD3 antibody. Exogenous interleukin-l did not deliver a costimulatory signal to these T cells, suggesting th at macrophage costimulatory activity was mediated through cell surface molecules. Modulation of the T cell responses by THC depended on the source of costimulation. THC did not suppress costimulatory activity p rovided by peritoneal macrophages or immobilized fibronectin. THC at l ow concentrations markedly diminished the costimulatory activity of a macrophage hybridoma to activate one T cell but not another. Inhibitio n of costimulation by THC inversely correlated with the loss of activi ty caused by paraformaldehyde fixation of macrophages, THC at 10(-8) M significantly decreased expression of costimulatory heat-stable antig en, which is resistant to fixation, on the macrophage hybridoma. Howev er, expression of co-stimulatory B7-1 and B7-2 molecules, which are se nsitive to fixation, was not affected by THC. Therefore, THC selective ly suppresses a fixation-resistant costimulatory signal to helper T ce lls in part by diminishing expression of heat-stable antigen.