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Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation

Toyokawa, H and Nakao, A and Bailey, RJ and Nalesnik, MA and Kaizu, T and Lemoine, JL and Ikeda, A and Tomiyama, K and Papworth, GD and Huang, L and Demetris, AJ and Starzi, TE and Murase, N (2008) Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation. Liver Transplantation, 14 (3). 346 - 357. ISSN 1527-6465

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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. © 2008 AASLD.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Toyokawa, H
Nakao, A
Bailey, RJ
Nalesnik, MAnalesnik@pitt.eduNALESNIK
Kaizu, T
Lemoine, JL
Ikeda, A
Tomiyama, K
Papworth, GD
Huang, L
Demetris, AJ
Starzi, TE
Murase, N
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 March 2008
Date Type: Publication
Journal or Publication Title: Liver Transplantation
Volume: 14
Number: 3
Page Range: 346 - 357
DOI or Unique Handle: 10.1002/lt.21378
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 1527-6465
Other ID: uls-drl:31735062121532, Starzl CV No. 2245
Date Deposited: 08 Apr 2010 17:38
Last Modified: 13 Jun 2021 01:55


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