DELTA(9)-TETRAHYDROCANNABINOL MODULATES ANTIGEN-PROCESSING BY MACROPHAGES

Delta(9)-Tetrahydrocannabinol (THC) exposure suppresses multiple immun ological functions of macrophages. The ability of macrophages exposed to THC to process and present soluble protein antigens was investigate d by the stimulation of antigen-specific helper T cell hybridomas to s ecrete interleukin-2. The T cell response to hen egg lysozyme was dram atically reduced after a 24-hr pretreatment of a macrophage hybridoma with THC. In contrast, THC exposure did not alter the capacity of the macrophage hybridoma to process chicken ovalbumin and augmented their presenting cell function for a pigeon cytochrome c response. These fin dings could not be attributed to differential effects of THC on either cell viability or expression of the antigen receptor-associated CD3 c omplex by the T cells. The level of T cell activation with peptides of lysozyme and cytochrome c, which do not require processing, was inhib ited only at the highest concentrations of THC, suggesting that THC ma inly affects antigen processing. Peritoneal macrophages exposed to THC during an antigen pulse and fixed with paraformaldehyde showed simila r effects on the subsequent T cell responses to lysozyme and cytochrom e c in the absence of THC, arguing against a possible influence of THC on the T cells. Therefore, THC differentially modulates the capacity of macrophages to process antigens that is necessary for the activatio n of CD4(+) T cells.