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Exploiting virus stealth technology for xenotransplantation: reduced human T cell responses to porcine cells expressing herpes simplex virus ICP47
Author(s) -
Crew Mark D.,
Phanavanh Bounleut
Publication year - 2003
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1034/j.1399-3089.2003.01116.x
Subject(s) - mhc class i , xenotransplantation , herpes simplex virus , major histocompatibility complex , biology , cd8 , cytotoxic t cell , microbiology and biotechnology , t cell , transfection , virology , immune system , cell culture , virus , immunology , transplantation , in vitro , genetics , medicine , surgery
Crew MD, Phanavanh B. Exploiting virus stealth technology for xenotransplantation: reduced human T cell responses to porcine cells expressing herpes simplex virus ICP47. Xenotransplantation 2003; 10: 50–59. © Blackwell Munksgaard, 2003 Direct recognition of porcine major histocompatibility complex (MHC) proteins by human T cells is well documented. Eliminating donor (porcine) MHC proteins may therefore be beneficial in pig‐to‐human xenotransplants. To this end, we have attempted to exploit viral stealth mechanisms to eliminate pig MHC class I cell‐surface expression. PK(15) (pig kidney) cells stably transfected with the herpes simplex virus (HSV) ICP47 gene [PK(15)‐ICP47 cells] exhibited a dramatic reduction of MHC class I cell‐surface expression when compared with untransfected PK(15) cells. To test the effect of down‐regulation of porcine MHC class I on human cellular immune responses, a human CD8+ enriched T cell line (anti‐PK15 T cells) with reactivity towards PK(15) cells was derived by repeated stimulation of human T cells with PK(15) cells stably transfected with the costimulatory molecule B7.1 [PK(15)‐B7.1 cells]. Anti‐PK15 T cells efficiently lyzed PK(15) cells but not PK(15)‐ICP47 (class I negative) cells. Consistent with effector function, anti‐PK15 T cells showed a robust proliferative response to PK(15)‐B7.1 cells but did not proliferate at all to PK(15)‐B7.1 cells which also expressed HSV ICP47. These results suggest that virus stealth technology can be exploited for xenotransplantation.