Silencing of HLA Class I Expression by Lentivirus Vector-mediated RNA interference results in resistance of primary cells to alloreactive Cell-mediat

Recent advances in vector technology now allow the possibility of genetically engineering graft tissues to express reduced levels of HLA. Reducing HLA expression could help to overcome the limitations imposed by polymorphisms which restrict availability of suitable donors, complicate logistics of procuring and delivering matched tissues and organs, and necessitate life-long immunosuppression. We have previously shown that lentiviral vectors can be used to deliver short hairpin RNAs (shRNA) that knock down HLA expression in a class- or allele-specific manner in established human cell lines, and thereby allow evasion from immune recognition by alloreactive T cells. Here we have further characterized and quantitated the effects of dose-dependent gene transfer and shRNA-mediated knockdown of HLA in human cell lines and primary cells on their ability to be recognized by alloreactive cytotoxic T lymphocytes (alloCTL).

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