DELTA-9-TETRAHYDROCANNABINOL SELECTIVELY INHIBITS T-CELL-DEPENDENT HUMORAL IMMUNE-RESPONSES THROUGH DIRECT INHIBITION OF ACCESSORY T-CELL FUNCTION

The major psychoactive and immunosuppressive component of marihuana, D ELTA9-tetrahydrocannabinol (DELTA9-THC), was investigated for its effe cts on primary humoral immune responses in the B6C3F1 mouse strain. Or al administration of 50-200 mg/kg DELTA9-THC produced a selective and dose related inhibition of primary humoral immune responses to the T-c ell dependent antigen, sRBC, as measured by the antibody forming cell (AFC) response with no inhibitory effect on humoral responses to the T -cell independent antigen, DNP-Ficoll. A similar profile of immune inh ibition was observed following in vitro direct addition of DELTA9-THC to naive spleen cell cultures sensitized with defined antigens. DELTA9 -THC produced a marked and dose related inhibition of the in vitro sRB C AFC response while having no inhibitory effects on T-cell independen t responses to either DNP-Ficoll or the polyclonal B-cell activator, l ipopolysaccharide. This selective inhibition of the sRBC response was not due to a shift in the peak day of response or a direct cytotoxic e ffect on spleen cells. In vivo kinetic studies demonstrated that inhib ition by DELTA9-THC of the sRBC response was most pronounced when drug administration occurred at times surrounding antigen sensitization. T o further evaluate the direct effect of DELTA9-THC on T-cell function, T-cell proliferative responses to stimulation by anti-CD3 monoclonal antibodies were measured. DELTA9-THC was found to produce a marked and dose related inhibition of anti-CD3 mAb-induced T-cell proliferation which was cell density dependent. These results suggest that suppressi on of humoral responses by DELTA9-THC may be mediated through early se lective inhibition of T-cell accessory function.