J Korean Soc Transplant.  2004 Dec;18(2):117-124.

Down-regulation of MHC class I Expression in Porcine Aortic Endothelial Cells by Introduction of hCMV US Genes

• Kim D
• Koh HS
• Kim JY
• Yang JS
• Park JH
• Park CG
• Ha J
• Kim SJ
• Lee JS
• Ahn C

Abstract

PURPOSE
Direct recognition of porcine MHC proteins by human T cells is an impediment to successful xenotransplantation. Therefore, reducing human T cell response initiated by the interaction between TCR/CD8 cell and MHC class I on pig endothelial cell may be beneficial in successful pig- to-human xenotransplantation.
METHODS
We examined MHC expression on porcine endothelial cell line, MYP30 cells in the absence or presence of IFN-g by FACS analysis. We introduced human cytomegalovirus (hCMV) US genes, which are known to be able to reduce MHC class I expression on the cell surface after infection, into MYP30 cells in order to test the feasibility of modifying these cells to reduced MHC class I antigens by the introduction of hCMV US genes such as US2, 3, 6 or 11.
RESULTS
MHC class I expressions in MYP30 cells were dramatically induced by IFN-gamma treatment. FACS analysis showed that cells transfected with the hCMV US2, 3, 6 or 11 genes exhibited 30~40% of MHC class I expression compared with mock-transfected cells. We next established stable cell lines expressing US6 gene, which had been found to exert best down-regulation effect on MHC class I expression. Stable cell line expressing US6 gene products exhibited more than 10% reduced expression level of the MHC class I compared with transiently transfected cells.
CONCLUSION
Although the further analysis of the cytotoxicities of T and NK cells on the hCMV US gene transfected cells are needed to clarify the feasibility of their application, these results suggest that virus stealth technology can be exploited for xenotransplantation.

Keyword

Porcine endothelial cell; Human CMV US gene; MHC class I

MeSH Terms

Cell Line
Cytomegalovirus
Down-Regulation*
Endothelial Cells*
Histocompatibility Antigens Class I
Humans
Killer Cells, Natural
T-Lymphocytes
Transplantation, Heterologous
Histocompatibility Antigens Class I