Porcine endogenous retrovirus encodes xenoantigens involved in porcine cellular xenograft rejection by mice.
BACKGROUND
Identification of the antigens that stimulate transplant rejection can help develop graft-specific antirejection strategies. The xenoantigens recognized during rejection of porcine cellular xenografts have not been clearly defined, but it has been assumed that major histocompatibility complex (MHC) xenoantigens are involved.


METHODS
The role of porcine endogenous retrovirus (PERV) as a source of xenoantigens was examined. The authors used morphometry to compare the kinetics of swine leukocyte antigen (SLA) pig thyroid xenograft rejection in control mice and mice immunized with PERV PK15 cells (porcine kidney epithelial cells), PERV SLA pig peripheral blood lymphocytes (PBL), PERV virions purified from PK15 cells, and PERV or PERV A pseudotypes produced from infected human 293 cells. The tempo of rejection for cellular xenografts of PERV A pseudotype-producing human 293 cells, uninfected human 293 cells, and PK15 cells in PERV-preimmunized and control mice was also compared.


RESULTS
Mice immunized with PK15 cells rejected pig thyroid xenografts significantly faster at day 5 than control mice and mice immunized with pig PBL. This correlated with the amount of PERV RNA and virions produced, but not with the amount of SLA class I MHC expressed by PK15 cells. Immunization of mice with PERV virions purified from porcine PK15 cells and with PERV virions or PERV A pseudotypes produced by human 293 cells also induced accelerated xenograft rejection by 5 days. Accelerated rejection induced by virus pretreatment was CD4 T-cell dependent and restricted to PERV-expressing cellular xenografts of porcine or nonporcine origin.


CONCLUSIONS
PERV acts as a significant source of xenoantigens that target porcine cellular xenografts for rejection.
Simeonovic
Charmaine J
CJ
Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University, PO Box 334, Canberra, ACT 2601, Australia. charmaine.simeonovic@anu.edu.au
Ziolkowski
Andrew F
AF
Popp
Sarah K
SK
Milburn
Peter J
PJ
Lynch
Celina-Ann
CA
Hamilton
Peter
P
Harris
Karla
K
Brown
Debra J
DJ
Bain
Simon A F
SA
Wilson
J Dennis
JD
Gibbs
Adrian J
AJ
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000302:isolation & purification*; D006084:Graft Rejection / Q000473:pathology / Q000821:virology*; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013556:Swine, Miniature; D013961:Thyroid Gland / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000473:pathology*; D014771:Virion / Q000235:genetics / Q000302:isolation & purification
D015478:Antigens, Heterophile; D000956:Antigens, Viral; D017931:DNA Primers