Prevention of suppression of alloreactive capacity following intravenous injection of neuraminidase-treated allogeneic cells by co-injection of agents competing for asialoglycoprotein receptor.
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.[1]References
- Prevention of suppression of alloreactive capacity following intravenous injection of neuraminidase-treated allogeneic cells by co-injection of agents competing for asialoglycoprotein receptor. Suda, T., Sano, S., Hori, S., Azuma, T., Tateishi, N., Hamaoka, T., Fujiwara, H. Regional immunology. (1988) [Pubmed]
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