Involvement of PD-L1 Upregulation in Anti-A/B Antibody-Induced Graft Accommodation: Reduction of CD4 T Cell Allo-Response against Graft HLA Class II DR
1Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
2Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
3Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Meeting: 2018 American Transplant Congress
Abstract number: B26
Keywords: Adhesion molecules, Alloantibodies, Endothelial cells, T cells
Session Information
Session Name: Poster Session B: Endothelial Cell Biology
Session Type: Poster Session
Date: Sunday, June 3, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
[Background] Antibodies against transplanted organs cause complement-independent graft injury, but there remain many unknown aspects of its mechanism, in particular its effect on allo-response to graft endothelial cells. In this study, the effect of anti-A/B antibody on CD4 T-cell allo-response to endothelial cell expressing HLA-DR was investigated.
[Method] CD4 T-cells were separated from human peripheral blood by negative selection and cultured with irradiated HLA -DR-induced endothelial cells. T-cell proliferation was evaluated by CFSE staining. For TCR gene analysis, OX40 positive cells were recovered after incubation for 48 hours and the CDR3α/β region at the single cell level was determined by 3 steps PCR. Microarray analysis was performed on endothelial cells collected after 48 hours of anti-A antibody ligation.
[Result] CD4 T-cells that proliferate by mixed culture of endothelial cells are mainly memory types such as Th1, Th2, Th17, and Tfh. TCR analysis demonstrated several highly reactive CD4 T-cell clones, and its proliferation was enhanced by anti-HLA class I, but attenuated by anti-A/B antibody. Microarray analysis showed that PD-L1 iwas upregulated by anti-A binding regardless of IFNγ. Anti-A antibody binding-induced attenuation of CD4 T-cell reaction was invalidated by anti-PD-1 antibody. In C4d-positive ABO-incompatible kidney grafts, PD-L1 was expressed at a higher level than in compatible grafts.
[Conclusion] Current study clearly showed a possibility that late direct-pathway responses could be modified by anti-donor antibodies, particularly reduced by anti-A/B antibodies. The elucidation of the mechanisms of late allo-response in the presence of donor antibody could be a new topic of organ transplantation.
CITATION INFORMATION: Iwasaki K., Miwa Y., Hamana H., Kishi H., Muraguchi A., Uchida K., Kobayashi T. Involvement of PD-L1 Upregulation in Anti-A/B Antibody-Induced Graft Accommodation: Reduction of CD4 T Cell Allo-Response against Graft HLA Class II DR Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Iwasaki K, Miwa Y, Hamana H, Kishi H, Muraguchi A, Uchida K, Kobayashi T. Involvement of PD-L1 Upregulation in Anti-A/B Antibody-Induced Graft Accommodation: Reduction of CD4 T Cell Allo-Response against Graft HLA Class II DR [abstract]. https://atcmeetingabstracts.com/abstract/involvement-of-pd-l1-upregulation-in-anti-a-b-antibody-induced-graft-accommodation-reduction-of-cd4-t-cell-allo-response-against-graft-hla-class-ii-dr/. Accessed June 1, 2025.« Back to 2018 American Transplant Congress