title: Cell-mediated cytotoxicity to porcine aortic endothelial cells is not dependent on galactosyl residues when baboon peripheral blood lymphocytes are previously primed with pig xenoantigens.
abstract: BACKGROUND
  In the pig-to-baboon model, acute vascular rejection remains the main hurdle for successful long-term xenograft survival. The production of galactosyl knockout pigs could solve concomitantly the problem of hyperacute and acute vascular rejection. This work studies in vitro the cell-mediated cytotoxicity of natural killer (NK) and T cells after priming of baboon peripheral blood lymphocytes (PBLs) with pig antigens to evaluate whether cytotoxicity is galactosyl-dependent.
  
  
  METHODS
  PBLs from naive and primed baboons were used as effectors on primary porcine aortic endothelial cells (PAECs) to assess cytotoxicity. Untreated or galactosidase-digested PAECs were used to evidence the role of galactosyl residues on cell-mediated cytotoxicity. Two rat-anti baboon monoclonal antibodies were tested to inhibit either T+NK cells (LO-CD2b) or NK cells alone (LO-CD94).
  
  
  RESULTS
  When using PBLs from naive animals, spontaneous lysis occurred and was inhibited by both LOCD-2b and LO-CD94. In comparison, lysis of PAECs was significantly higher when baboon PBLs were first primed in vivo with pig xenoantigens. In this case, cytotoxicity was completely inhibited by LO-CD2b but only partially by LO-CD94. Reduction of galactosyl residues by galactosidase digestion showed that PAEC lysis almost completely disappeared with naive baboon PBLs but not with primed baboon PBLs, thereby indicating that anti-pig T-cell response is not dependent on galactosyl residues.
  
  
  CONCLUSIONS
  Galactosyl knockout pigs could solve hyperacute rejection and also prevent the activation of NK cells even after xenogeneic priming. T cells will then be the next hurdle for the success of xenografting.
authors.affiliation: Laboratory of Experimental Surgery, Faculty of Medicine, Université Catholique de Louvain, CHEX/5570, 55 Avenue Hippocrate, B-1200 Brussels, Belgium.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Dehoux
authors.forename: Yannick
authors.initials: Y
authors.lastname: Nizet
authors.forename: Bernardo
authors.initials: B
authors.lastname: de la Parra
authors.forename: Corinne
authors.initials: C
authors.lastname: Lecuivre
authors.forename: Martial
authors.initials: M
authors.lastname: Vergauwen
authors.forename: Hervé
authors.initials: H
authors.lastname: Bazin
authors.forename: Dominique
authors.initials: D
authors.lastname: Latinne
authors.forename: Pierre
authors.initials: P
authors.lastname: Gianello
mesh_terms: D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D001011:Aorta; D002470:Cell Survival; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D007074:Immunoglobulin G / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D023421:Models, Animal; D010215:Papio; D051381:Rats; D013552:Swine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods; D014183:Transplantation, Heterologous / Q000276:immunology*; D000519:alpha-Galactosidase
chemical_list: D015478:Antigens, Heterophile; D007074:Immunoglobulin G; D000519:alpha-Galactosidase