Human leukocyte antigen-DR matching improved skin graft survival from transgenic pigs to accommodate SCID mice reconstituted with human peripheral blood mononuclear cells.
The shortage of human organs has encouraged scientists to develop genetically modified pigs for xenotransplantation, such as CD55 or CD46, and CD59 transgenesis as well as alpha-galactosyl transferase gene knockouts. In allotransplantation, the match of human leukocyte antigen class II (HLA-II) may improve graft survival although the role of HLA-II in xenotransplantation is unknown. HLA-II transgenic pigs, including DP, DQ, and DR, have been successfully generated and HLA-DR15+ transgenic pig skin pieces grafted onto severe congenital immunodeficiency (SCID) mice reconstituted intraperitoneally with HLA-DR15+ or HLA-DR15(-) human peripheral blood mononuclear cells (hPBMCs). This study sought to develop an animal model to evaluate the effects of HLA-DR matching on xenograft survival. Human CD4+ and CD8+ were detected from days 7 to 29 after hPBMC reconstitution in SCID mice. Both CD4+ and CD8+ cells of HLA-DR15(-) reconstituted SCID mice were significantly higher at day 29 postgrafting compared with HLA-DR15+ reconstituted SCID mice. An HLA-DR15+ transgenic pig dermal graft survived and integrated into SCID mice reconstituted with hPBMCs/HLA-DR15+ as proven by the histopathological finding that the collagen layer remained intact with little lymphocytic response. In contrast, the transgenic pig dermal graft showed more collagen disruption as well as mild to moderate lymphocytic infiltration when reconstituted in an hPBMC/HLA-DR15(-) SCID mouse. The results suggested that HLA-DR matching eased xenograft rejection; however, it was not yet clear that the response was mediated by T cells.
Tu
C-F
CF
Division of Biotechnology, Animal Technology Institute Taiwan, Taiwan, Republic of China. cftu@mail.atit.org.tw
Tai
H-C
HC
Chen
C-M
CM
Huang
T-T
TT
Lee
J-M
JM
Yang
T-S
TS
Chen
C-H
CH
Tseng
Y-L
YL
Chou
N-K
NK
Lee
P-H
PH
D000818:Animals; D030801:Animals, Genetically Modified; D006085:Graft Survival / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D051379:Mice; D016513:Mice, SCID; D016038:Skin Transplantation / Q000276:immunology*; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D006684:HLA-DR Antigens