title: Prevention of suppression of alloreactive capacity following intravenous injection of neuraminidase-treated allogeneic cells by co-injection of agents competing for asialoglycoprotein receptor.
abstract: Intravenous (i.v.) administration of neuraminidase (Nase)-treated allogeneic lymphocytes resulted in the complete abrogation of the capacity to develop delayed-type hypersensitivity (DTH) responses to the relevant alloantigens (tolerance induction). The Nase treatment did not influence the antigenicity of allogeneic lymphocytes, as subcutaneous inoculation of Nase-treated cells was capable of generating comparable anti-allo-DTH responses to those induced by untreated allogeneic cells. However, Nase-treated lymphocytes were revealed to exhibit strikingly enhanced reactivity to the lectin peanut agglutinin (PNA) as well as adhesion to hepatocytes in the primary culture. Such enhanced PNA-reactivity was inhibited by lactose but not by maltose, and enhanced hepatocyte-adhesion was also inhibited by N-acetyl-galactosamine (GalNAc) but not by N-acetyl-glucosamine (GlcNAc), indicating augmented reactivity of Nase-treated cells to Gal/GalNAc-specific receptors on hepatocytes. It was also demonstrated that i.v. infusion of Nase-treated, 51Cr-labeled lymphocytes leads to an increased radioactivity in the liver and that this enhanced retention of radioactivity can be inhibited by the co-injection of Nase-treated, unlabeled syngeneic erythrocytes. Most importantly, the co-injection of Nase-treated allogeneic lymphocytes and Nase-treated erythrocytes resulted in the prevention of the suppression of anti-allo-DTH responses as induced by the injection of Nase-treated allogeneic cells alone. These results indicate that Nase-treated allogeneic cells are entrapped in the liver in a strikingly increased way through their enhanced reactivity to Gal/GAlNAc receptor of the liver and suggest that such enhanced entrapment by the liver has a crucial role in inducing anti-allo-DTH tolerance.
authors.affiliation: Department of Oncogenesis, Osaka University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Suda
authors.forename: S
authors.initials: S
authors.lastname: Sano
authors.forename: S
authors.initials: S
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Azuma
authors.forename: N
authors.initials: N
authors.lastname: Tateishi
authors.forename: T
authors.initials: T
authors.lastname: Hamaoka
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor; D002478:Cells, Cultured; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007108:Immune Tolerance; D007519:Isoantigens / Q000276:immunology; D037102:Lectins / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009439:Neuraminidase / Q000494:pharmacology*; D019887:Peanut Agglutinin; D011971:Receptors, Immunologic / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects
chemical_list: D037263:Asialoglycoprotein Receptor; D007519:Isoantigens; D037102:Lectins; D019887:Peanut Agglutinin; D011971:Receptors, Immunologic; D009439:Neuraminidase