PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft

M. Morita, M. Fujino, G. Jiang, Y. Kitazawa, L. Xie, M. Azuma, H. Yagita, Shizuko Nagao, A. Sugioka, Y. Kurosawa, S. Takahara, J. Fung, S. Qian, L. Lu, X. K. Li

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Abstract

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.

Original languageEnglish
Pages (from-to)40-46
Number of pages7
JournalAmerican Journal of Transplantation
Volume10
Issue number1
DOIs
Publication statusPublished - 01-01-2010

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Allografts
Liver
Apoptosis
Homologous Transplantation
Knockout Mice
Liver Transplantation
Necrosis
Up-Regulation
Tissue Donors
T-Lymphocytes
Messenger RNA
Mortality
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Morita, M. ; Fujino, M. ; Jiang, G. ; Kitazawa, Y. ; Xie, L. ; Azuma, M. ; Yagita, H. ; Nagao, Shizuko ; Sugioka, A. ; Kurosawa, Y. ; Takahara, S. ; Fung, J. ; Qian, S. ; Lu, L. ; Li, X. K. / PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft. In: American Journal of Transplantation. 2010 ; Vol. 10, No. 1. pp. 40-46.
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Morita, M, Fujino, M, Jiang, G, Kitazawa, Y, Xie, L, Azuma, M, Yagita, H, Nagao, S, Sugioka, A, Kurosawa, Y, Takahara, S, Fung, J, Qian, S, Lu, L & Li, XK 2010, 'PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft', American Journal of Transplantation, vol. 10, no. 1, pp. 40-46. https://doi.org/10.1111/j.1600-6143.2009.02859.x

PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft. / Morita, M.; Fujino, M.; Jiang, G.; Kitazawa, Y.; Xie, L.; Azuma, M.; Yagita, H.; Nagao, Shizuko; Sugioka, A.; Kurosawa, Y.; Takahara, S.; Fung, J.; Qian, S.; Lu, L.; Li, X. K.

In: American Journal of Transplantation, Vol. 10, No. 1, 01.01.2010, p. 40-46.

Research output: Contribution to journalArticle

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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, Shizuko

AU - Sugioka, A.

AU - Kurosawa, Y.

AU - Takahara, S.

AU - Fung, J.

AU - Qian, S.

AU - Lu, L.

AU - Li, X. K.

PY - 2010/1/1

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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.

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