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.
Transplantation
; 76(12): 1675-80, 2003 Dec 27.
Article
em En
| MEDLINE
| ID: mdl-14688514
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. MATERIAL ANDMETHODS:
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.CONCLUSION:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante Heterólogo
/
Imunoglobulina G
/
Endotélio Vascular
/
Linfócitos
/
Linfócitos T Citotóxicos
/
Antígenos Heterófilos
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article