RRC ID 62695
Author Ueta H, Xu XD, Yu B, Kitazawa Y, Yu E, Hara Y, Morita-Nakagawa M, Zhou S, Sawanobori Y, Ueha S, Rokutan K, Tanaka T, Tokuda N, Matsushima K, Matsuno K.
Title Suppression of liver transplant rejection by anti-donor MHC antibodies via□ depletion of donor immunogenic dendritic cells.
Journal Int Immunol
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, tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC 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 and DST pretreatments 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 recipient Treg proliferative response, 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 pathway 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.
Published 2020-12-1
DOI 10.1093/intimm/dxaa076
PII 6015059
PMID 33258927
Rats ACI/NKyo (StrainID=6)