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Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation
Author(s) -
Toyokawa Hideyoshi,
Nakao Atsunori,
Bailey Robert J.,
Nalesnik Michael A.,
Kaizu Takashi,
Lemoine Jerome L.,
Ikeda Atsushi,
Tomiyama Koji,
Papworth Glenn D.,
Huang Leaf,
Demetris Anthony J.,
Starzl Thomas E.,
Murase Noriko
Publication year - 2008
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21378
Subject(s) - allorecognition , immunology , medicine , liver transplantation , transplantation , major histocompatibility complex , immune tolerance , t cell , immune system , cd11c , dendritic cell , priming (agriculture) , biology , biochemistry , phenotype , gene , botany , germination
The interaction of donor passenger leukocytes and host leukocytes in recipient secondary lymphoid tissues during the early posttransplantation period is crucial in directing host immune reactions toward allograft rejection or acceptance. Responsible T cell clones could be activated through the direct and indirect pathways of allorecognition. We examined the role of the indirect pathway in liver transplantation (LT) tolerance by depleting host antigen‐presenting cells (APC) with phagocytic activity [e.g., cluster domain (CD)68 + /CD163 + macrophages, CD11c + dendritic cells (DC)] using liposome‐encapsulating clodronate (LP‐CL). After Lewis rat cell or liver graft transplantation, Brown Norway (BN) rat recipients pretreated with LP‐CL showed a significantly reduced type 1 helper T cell cytokine up‐regulation than control‐LP‐treated recipients. In the LT model, LP‐CL treatment and host APC depletion abrogated hepatic tolerance; Lewis liver grafts in LP‐CL‐treated‐BN recipients developed mild allograft rejection, failed to maintain donor major histocompatibility complex (MHC) class II + leukocytes, and developed chronic rejection in challenged donor heart allografts, while control‐LP‐treated BN recipients maintained tolerance status and donor MHC class II + hepatic leukocytes. Furthermore, in the BN to Lewis LT model, LP‐CL recipient treatment abrogated spontaneous hepatic allograft acceptance, and graft survival rate was reduced to 43% from 100% in the control‐LP group. In conclusion, the study suggests that host cells with phagocytic activity could play significant roles in developing LT tolerance. Liver Transpl 14:346–357, 2008. © 2008 AASLD.