Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by Delta(9)-tetrahydrocannabinol

作者：Springs Alison E B; Karmaus Peer W F; Crawford Robert B; Kaplan Barbara L F; Kaminski Norbert E^*

来源：Journal of Leukocyte Biology, 2008, 84(6): 1574-1584.

DOI：10.1189/jlb.0508282

• immunopharmacology
• CD40 ligand
• humoral immunity
• cell-mediated immunity

The role of cannabinoid receptors, CB1 and CB2, in immune competence and modulation by Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was investigated in CB1(-/-)/ CB2-/- mice. Immunofluorescence analysis of splenic leukocytes showed no significant differences in the percentage of T cell subsets, B cells, or macrophages between wild-type and CB1-/-/CB2-/- mice. Lymphoproliferative control responses to PHA, phorbol ester plus ionomycin, or LPS and sensitivity to suppression by Delta(9)-THC showed no profound differences between the two genotypes, although some differences were observed in control baseline responses. Likewise, similar control responses and sensitivity to Delta(9)-THC were observed in mixed lymphocyte responses (MLR) and in IL-2 and IFN-gamma production in both genotypes. Conversely, humoral immune responses showed a markedly different profile of activity. Delta(9)-THC suppressed the in vivo T cell-dependent, anti-sheep RBC ( anti-sRBC) IgM antibody-forming cell (AFC) response in wild- type but not in CB1-/-/CB2-/- mice, and the in vitro anti-sRBC IgM response in CB1-/-/ CB2-/- splenocytes was too low to rigorously assess CB1/CB2 involvement in modulation by Delta(9)-THC. Conversely, comparable in vitro IgM AFC control responses to LPS and CD40 ligand (CD40L) activation were observed in the two genotypes. Interestingly, LPS-induced IgM responses were refractory to suppression by Delta(9)-THC, regardless of genotype, and CD40L-induced IgM responses were only suppressed by Delta(9)-THC in wildtype but not in CB1-/-/CB2-/- B cells. Collectively, we demonstrate differential involvement of CB1 and/or CB2 in immune modulation by Delta(9)-THC and in some control responses. Moreover, CB1/CB2 involvement was observed in humoral responses requiring CD40- initiated signaling for suppression by Delta(9)-THC. J. Leukoc. Biol. 84: 1574-1584; 2008.

• 出版日期2008-12-1