The delta-opioid receptor participates in T-cell development by promoting negative selection.
The delta-opioid receptor-1 (DOR-1) as well as delta-opioid enkephalin peptides are expressed during maturation of T cells, although the functional significance of their expression remains unclear. Based on results which show that the administration of the highly selective delta-opioid agonist D-Pen2, D-Pen5]enkephalin (DPDPE) induces an altered pattern of T-cell differentiation in fetal thymic organ culture (FTOC), we hypothesized that DOR-1 is involved in the negative selection process. Our results show that superantigen-induced clonal deletion is promoted by DPDPE and significantly impaired in DOR-1-deficient mice. These results suggest that delta-opioids may play a homeostatic role in the negative selection process during T-cell development.
McCarthy
Lois E
LE
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Nitsche
Joshua F
JF
Pintar
John E
JE
Rogers
Thomas J
TJ
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004723:Endorphins / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology*; D004768:Enterotoxins / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009924:Organ Culture Techniques; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects
D000701:Analgesics, Opioid; D015704:CD4 Antigens; D016827:CD8 Antigens; C470381:DOR-1 protein, mouse; D004723:Endorphins; D004768:Enterotoxins; D009292:Narcotic Antagonists; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017465:Receptors, Opioid, delta; C113249:T cell receptor peptide Vbeta8.1; D009270:Naloxone; C031818:enterotoxin B, staphylococcal; C024770:alpha-endorphin, des-Tyr(1)-; D020881:Enkephalin, D-Penicillamine (2,5)-