1. Suppression of liver transplant rejection by anti-donor MHC antibodies via depletion of donor immunogenic dendritic cells
- Author
-
Kenjiro Matsuno, Shu Zhou, Enqiao Yu, Bin Yu, Xue Dong Xu, Kouji Matsushima, Nobuko Tokuda, Yasushi Sawanobori, Kazuhito Rokutan, Satoshi Ueha, Hisashi Ueta, Yoshiaki Hara, Yusuke Kitazawa, Toshiya Tanaka, and Miwa Morita-Nakagawa
- Subjects
0301 basic medicine ,Graft Rejection ,medicine.medical_treatment ,Immunology ,AcademicSubjects/MED00730 ,chemical and pharmacologic phenomena ,CD8 T cells ,030230 surgery ,Liver transplantation ,CD8-Positive T-Lymphocytes ,Major histocompatibility complex ,T-Lymphocytes, Regulatory ,Animals, Genetically Modified ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Isoantibodies ,medicine ,Immune Tolerance ,sensitization pathway ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Transplantation, Homologous ,Allorecognition ,leukocyte trafficking ,CD11b Antigen ,biology ,Chemistry ,multicolor immunohistochemistry ,Graft Survival ,Histocompatibility Antigens Class I ,General Medicine ,Dendritic cell ,Dendritic Cells ,Antigens, Differentiation ,Tissue Donors ,Liver Transplantation ,Rats ,Editor's Choice ,030104 developmental biology ,Rats, Inbred Lew ,Antibody Formation ,biology.protein ,Featured Article of the Month ,Antibody ,CD8 ,donor-specific transfusion - Abstract
Background We previously found two distinct passenger dendritic cell (DC) subsets in the rat liver that played a central role in the liver transplant rejection. In addition, a tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC (MHCI) antigen (DST-antibodies). Methods We examined the role of DST-antibodies in the trafficking of graft DC subsets and the alloresponses in a rat model. We also examined an anti-donor class II MHC (MHCII) antibody that recognizes donor DCs more selectively. Results Preoperative transfer of DST-antibodies or DST pretreatment eliminated all passenger leukocytes, including both DC subsets and depleted the sessile DCs in the graft to ~20% of control. The CD172a+CD11b/c+ immunogenic subset was almost abolished. The intrahost direct or semi-direct allorecognition pathway was successfully blocked, leading to a significant suppression of the CD8+ T-cell response in the recipient lymphoid organs and the graft with delayed graft rejection. Anti-donor MHCII antibody had similar effects without temporary graft damage. Although DST pretreatment had a priming effect on the proliferative response of recipient regulatory T cells, DST-primed sera and the anti-donor MHCII antibody did not. Conclusion DST-antibodies and anti-donor MHCII antibodies could suppress the CD8+ T-cell-mediated liver transplant rejection by depleting donor immunogenic DCs, blocking the direct or semi-direct pathways of allorecognition. Donor MHCII-specific antibodies may be applicable as a selective suppressant of anti-donor immunity for clinical liver transplantation without the cellular damage of donor MHCII– graft cells and recipient cells., Antibody-mediated donor-DC depletion prolongs liver-graft survival
- Published
- 2020