Δ9-tetrahydrocannabinol selectivity inhibits T-cell dependent humoral immune responses through direct inhibition of accessory T-cell function

Abstract

The major psychoactive and immunosuppressive component of marihuana, Δ9-tetrahydrocannabinol (Δ9-THC), was investigated for its effects on primary humoral immune responses in the B6C3F1 mouse strain. Oral administration of 50–200 mg/kg Δ9-THC produced a selective and dose related inhibition of primary humoral immune responses to the T-cell 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 inhibition was observed following in vitro direct addition of Δ9-THC to naive spleen cell cultures sensitized with defined antigens. Δ9-THC produced a marked and dose related inhibitio n of the in vitro sRBC AFC response while having no inhibitory effects on T-cell independent responses to either DNP-Ficoll or the polyclonal B-cell activator, lipopolysaccharide. This selective inhibition of the sRBC response was not due to a shift in the peak day of response or a direct cytotoxic effect on spleen cells. In vivo kinetic studies demonstrated that inhibition by Δ9-THC of the sRBC response was most pronounced when drug administration occured at times surrounding antigen sensitation. To further evaluate the direct effect of Δ9-THC on T-cell function, T-cell proliferative responses to stimulation by anti-CD3 monoclonal antibodies were measured. Δ9-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 suppression of humoral responses by Δ9-THC may be mediated through early selective inhibition of T-cell accessory function.