TY - JOUR
T1 - PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft
AU - Morita, M.
AU - Fujino, M.
AU - Jiang, G.
AU - Kitazawa, Y.
AU - Xie, L.
AU - Azuma, M.
AU - Yagita, H.
AU - Nagao, S.
AU - Sugioka, A.
AU - Kurosawa, Y.
AU - Takahara, S.
AU - Fung, J.
AU - Qian, S.
AU - Lu, L.
AU - Li, X. K.
PY - 2010/1
Y1 - 2010/1
N2 - The programmed death-1 (PD-1)/B7-H1 pathway acts as an important negative regulator of immune responses. We herein investigated the role of the PD-1/B7-H1 pathway in establishing an immunological spontaneous tolerance status in mouse liver allografting. B7-H1 is highly expressed on the donor-derived tissue cells and it is also associated with the apoptosis of infiltrating T cells in the allografts. Strikingly, a blockade of the PD-1/B7-H1 pathway via anti-B7-H1mAb or using B7-H1 knockout mice as a donor led to severe cell infiltration as well as hemorrhaging and necrosis, thus resulting in mortality within 12 days. Furthermore, the expression of the FasL, perforin, granzyme B, iNOS and OPN mRNA in the liver allografts increased in the antibody-treated group in comparison to the controls. Taken together, these data revealed that the B7-H1 upregulation on the tissue cells of liver allografts thus plays an important role in the apoptosis of infiltrating cells, which might play a critical role of the induction of the spontaneous tolerance after hepatic transplantation in mice.
AB - The programmed death-1 (PD-1)/B7-H1 pathway acts as an important negative regulator of immune responses. We herein investigated the role of the PD-1/B7-H1 pathway in establishing an immunological spontaneous tolerance status in mouse liver allografting. B7-H1 is highly expressed on the donor-derived tissue cells and it is also associated with the apoptosis of infiltrating T cells in the allografts. Strikingly, a blockade of the PD-1/B7-H1 pathway via anti-B7-H1mAb or using B7-H1 knockout mice as a donor led to severe cell infiltration as well as hemorrhaging and necrosis, thus resulting in mortality within 12 days. Furthermore, the expression of the FasL, perforin, granzyme B, iNOS and OPN mRNA in the liver allografts increased in the antibody-treated group in comparison to the controls. Taken together, these data revealed that the B7-H1 upregulation on the tissue cells of liver allografts thus plays an important role in the apoptosis of infiltrating cells, which might play a critical role of the induction of the spontaneous tolerance after hepatic transplantation in mice.
KW - Apoptosis
KW - B7-H1
KW - Orthotopic liver transplantation
KW - Regulatory cell
KW - Spontaneous tolerance
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U2 - 10.1111/j.1600-6143.2009.02859.x
DO - 10.1111/j.1600-6143.2009.02859.x
M3 - Article
C2 - 19889124
AN - SCOPUS:72549114816
SN - 1600-6135
VL - 10
SP - 40
EP - 46
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 1
ER -