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

Hideyoshi Toyokawa, Atsunori Nakao, Robert J. Bailey, Michael A. Nalesnik, Takashi Kaizu, Jerome L. Lemoine, Atsushi Ikeda, Koji Tomiyama, Glenn D. Papworth, Leaf Huang, Anthony J. Demetris, Thomas E. Starzi, Noriko Murase

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)346-357
Number of pages12
JournalLiver Transplantation
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

Fingerprint

Clodronic Acid
Liposomes
Liver Transplantation
Allografts
Leukocytes
Norway
Transplantation Tolerance
Liver
Antigen-Presenting Cells
Major Histocompatibility Complex
Transplants
Th1 Cells
Lymphoid Tissue
Graft Survival
Phagocytes
Dendritic Cells
Up-Regulation
Clone Cells
Macrophages
Cytokines

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation. / 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.; Starzi, Thomas E.; Murase, Noriko.

In: Liver Transplantation, Vol. 14, No. 3, 03.2008, p. 346-357.

Research output: Contribution to journalArticle

Toyokawa, H, Nakao, A, Bailey, RJ, Nalesnik, MA, Kaizu, T, Lemoine, JL, Ikeda, A, Tomiyama, K, Papworth, GD, Huang, L, Demetris, AJ, Starzi, TE & Murase, N 2008, 'Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation', Liver Transplantation, vol. 14, no. 3, pp. 346-357. https://doi.org/10.1002/lt.21378
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. ; Starzi, Thomas E. ; Murase, Noriko. / Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation. In: Liver Transplantation. 2008 ; Vol. 14, No. 3. pp. 346-357.
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