Antibody response and allogeneic mixed lymphocyte reaction in mu-, delta-, and kappa-opioid receptor knockout mice.
The implication of opioid receptors in immune response has been studied using mu-, delta- and kappa-opioid receptor knockout mice. The mutant animals were compared to their wild-type (WT) counterparts for antibody (Ab) response to the prototype Ag keyhole limpet hemocyanin (KLH). Kappa-receptor deficient mice displayed higher Ab titers for either total Ig, IgM, IgG1 or IgG2a isotypes, whereas mu and delta animals behaved as wild-type mice. Therefore, endogenous kappa-receptor activation would tonically inhibit Ab response. Opioid receptor deficient mice were also used to investigate the immunosuppressive action of naltrindole, a delta-opioid receptor antagonist, shown earlier to inhibit graft rejection and the allogeneic mixed lymphocyte reaction (MLR) in vitro. Naltrindole and two related compounds inhibited MLR performed with lymphocytes from wild-type and delta-opioid receptor knockout mice. These compounds also suppressed MLR assayed with cells from triple mu/delta/kappa-opioid receptor mutants. We therefore demonstrate that naltrindole immunosuppressive activity is not mediated by any of the three mu-, delta- or kappa-opioid receptors, but by a target which remains to be discovered.
Gaveriaux-Ruff
C
C
Department of Neurobiology, Institute de Genetique et de Biologie Moleculaire et Cellular, BP 163, CU de Strasborg, 67404 Illkirch cedex, France. gaveriau@titus.u-strasbg.fr
Simonin
F
F
Filliol
D
D
Kieffer
B
B
D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D006084:Graft Rejection; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout / Q000276:immunology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011957:Receptors, Opioid / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009271:Naltrexone; C055382:naltrindole