| First Author | Springs AE | Year | 2008 |
| Journal | J Leukoc Biol | Volume | 84 |
| Issue | 6 | Pages | 1574-84 |
| PubMed ID | 18791168 | Mgi Jnum | J:142602 |
| Mgi Id | MGI:3821813 | Doi | 10.1189/jlb.0508282 |
| Citation | Springs AE, et al. (2008) Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by {Delta}9-tetrahydrocannabinol. J Leukoc Biol 84(6):1574-84 |
| abstractText | The role of cannabinoid receptors, CB(1) and CB(2), in immune competence and modulation by Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was investigated in CB(1)(-/-)/CB(2)(-/-) 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 CB(1)(-/-)/CB(2)(-/-) 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 CB(1)(-/-)/CB(2)(-/-) mice, and the in vitro anti-sRBC IgM response in CB(1)(-/-)/CB(2)(-/-) splenocytes was too low to rigorously assess CB(1)/CB(2) 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 wild-type but not in CB(1)(-/-)/CB(2)(-/-) B cells. Collectively, we demonstrate differential involvement of CB(1) and/or CB(2) in immune modulation by Delta(9)-THC and in some control responses. Moreover, CB(1)/CB(2) involvement was observed in humoral responses requiring CD40-initiated signaling for suppression by Delta(9)-THC. |
