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B7H1 Expression is Crucial for Tolerance Induction in Mouse Liver Transplantation

M. Morita1, S. Datta1, C. Miller2, T. Hamilton1, K. Hashimoto3

1Inflammation & Immunity, Lerner Research Institution, Cleveland, OH, 2General surgery, Liver Transplant Center, Cleveland Clinic, Cleveland, OH, 3General Surgery, Liver Transplant Center, Cleveland Clinic, Cleveland, OH

Meeting: 2019 American Transplant Congress

Abstract number: D48

Keywords: Co-stimulation, Liver transplantation, Tolerance

Session Information

Session Name: Poster Session D: Tolerance / Immune Deviation

Session Type: Poster Session

Date: Tuesday, June 4, 2019

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Following organ transplantation, lifelong immunosuppressive treatment is required and it causes severe side effects. Induction of donor specific tolerance is ideal, which actually spontaneously occurs following liver transplantation in many species. In mice,liver allograft can be accepted across fully mismatched MHC without immunosuppressive drugs. But the mechanism remains unclear. We have previously identified the importance of B7-H1 expression in spontaneous allograft acceptance. In this study, we examined the kinetics of B7H1 expression after liver transplantation and its impact on graft acceptance.

*Methods: C57BL/10(H2b) and C3H/HeJ(H2k) mice were used for liver transplantation as donor and recipient, respectively. B7H1 expression was measured from graft non-parenchymal cells, 0, 3, 7, 14, 21, and 80 days after transplantation using isolated RNA subjected to quantitative PCR analysis. The expression on immune cells like CD31+, CD19+, CD4+, CD8+, F4/80+, CD11b+, and CD11c+ cells were analyzed with flow cytometry. To identify the time point of B7H1 expression, crucial for graft acceptance, anti-B7H1/isotype control antibody was administered to recipients from day 0, 3, 7, 14, 80 days after transplantation (0.2mg/dose, on day 0, 1, thereafter twice a week, i.p.) for two weeks, and their survival days and histological changes were examined and compared with controls.

*Results: Among the different non-parenchymal cell populations, CD31+, CD11b+, and F4/80+ cells showed maximum expression of B7H1 on day 3 after transplantation. Similar outcome was also observed from the qPCR data, while the expression on CD4+, CD8+, and, CD19+ didn’t change after transplantation. Mice subjected to anti-B7H1 antibody treatment, 0 and 3 days post- transplant showed 100 % mortality within five to six days, whereas, mortality was 66% for mice receiving treatment 7 days post-transplant. Interestingly, all recipients treated day 14 and 80 post -transplant survived more than 14 days after treatment.Histological findings of liver grafts treated with anti-B7H1 antibody on day 0 and 3, showed diffused lymphocytes infiltration indicating severe rejection pattern when compared with isotype control which showed typical lymphocytes accumulation around portal triad.

*Conclusions: B7H1 expression at early phase of liver transplantation is crucial for tolerance induction associated with its expression on endothelial cells, myeloid cells and Kupffer cells. But it is not important for maintenance of tolerance.

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To cite this abstract in AMA style:

Morita M, Datta S, Miller C, Hamilton T, Hashimoto K. B7H1 Expression is Crucial for Tolerance Induction in Mouse Liver Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/b7h1-expression-is-crucial-for-tolerance-induction-in-mouse-liver-transplantation/. Accessed May 12, 2025.

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