title: Immune conditions associated with CD4+ T effector-induced opioid release and analgesia.
abstract: Effector CD4(+) T lymphocytes generated in response to antigens produce endogenous opioids. Thus, in addition to their critical role in host defenses against pathogens, effector CD4(+) T lymphocytes contribute to relieving inflammatory pain. In this study, we investigated mechanisms of opioid release by antigen-experienced effector CD4(+) T cells that leave draining lymph nodes and come back into the inflammatory site. Effector antigen-primed CD4(+) T lymphocytes generated in vitro were intravenously injected into nude mice previously immunized with either cognate or irrelevant antigens in complete Freund adjuvant (CFA). CFA-induced mechanical hyperalgesia was only reduced in mice immunized with cognate antigen. Thus, antinociceptive activity of effector CD4(+) T cells requires the presence of the antigen for which they are specific within the inflammatory site. Accordingly, analgesia was inhibited by neutralizing cognate T cell receptor-mediated interaction between effector CD4(+) T lymphocytes and antigen-presenting cells at the site of inflammation. Analgesia was observed by transferring effector CD4(+) T lymphocytes with Th1 or Th2 phenotype, suggesting that antinociceptive activity is a fundamental property of effector CD4(+) T lymphocytes irrespective of their effector functions. Based on the use of agonists and antagonists selective for each of the opioid receptor subclasses, we showed that analgesia induced by T cell-derived opioids is elicited via activation of δ-type opioid receptors in the periphery. Thus, the antinociceptive activity is a fundamental property associated with the effector phase of adaptive immunity, which is driven by recognition of the cognate antigen by effector CD4(+) T lymphocytes at the inflammatory site.
authors.affiliation: INSERM, U1043, Toulouse, France CNRS, U5282, Toulouse, France Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boué
authors.forename: Catherine
authors.initials: C
authors.lastname: Blanpied
authors.forename: Marilena
authors.initials: M
authors.lastname: Djata-Cabral
authors.forename: Lucette
authors.initials: L
authors.lastname: Pelletier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.forename: Gilles
authors.initials: G
authors.lastname: Dietrich
mesh_terms: D056704:Adaptive Immunity; D000698:Analgesia / Q000379:methods*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004745:Enkephalins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018847:Opioid Peptides / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010146:Pain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011498:Protein Precursors / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D004745:Enkephalins; D018847:Opioid Peptides; D011498:Protein Precursors; C029992:proenkephalin