Long-term survival of HLA-DR15+ pig skin in SCID mice after reconstitution with human peripheral blood mononuclear cells and under short-term immunosuppression.
In allotransplantation, donor-recipient human leukocyte antigen (HLA) matches improve graft survival. For studies of the role of donor-recipient HLA II matching on xenotransplantation, we successfully generated HLA-DR15+ transgenic pigs the the skins of which were transplanted to SCID mice, which were thereafter reconstituted with HLA-DR15+ or -DR15(-) hPBMC. Cyclosporine was given intraperitoneally to SCID mice for 12 days. Human T cells were observed in SCID mice after reconstitution. Mixed lymphocytes responses showed greater responses by HLA-DR15(-) human peripheral blood mononuclear cells (hPBMC) against HLA-DR15+ porcine PBMC. HLA-DR15+ porcine skins survived more than 100 days in all SCID mice. HLA-DR15+ porcine skins were rejected in all non-SCID (Balb/c) mice. The histologic pictures of transplanted HLA-DR15+ porcine skins showed surviving porcine epithelium in remodeling murine dermis and little lymphocyte infiltration into the murine dermis. The long-term survival of HLA-DR15+ pig skin in all hPBMC-SCID mice might be due to poor engraftment or function of reconstituted T cells. Further studies are needed to clarify the role of donor-recipient matching of HLA-DR15.
Tai
H-C
HC
Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
Tu
C-F
CF
Lee
J-M
JM
Ho
L-L
LL
Tseng
Y-L
YL
Chou
N-K
NK
Yang
T-S
TS
Weng
C-N
CN
Lee
P-H
PH
Chang
K-J
KJ
Tang
Y-B
YB
D000818:Animals; D006085:Graft Survival / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D007165:Immunosuppression Therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D012867:Skin / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D013552:Swine
D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen