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Early passenger leukocyte migration and acute immune reactions in the rat recipient spleen during liver engraftment: With particular emphasis on donor major histocompatibility complex class II<sup>+</sup> cells

Okuda, T and Ishikawa, T and Azhipa, O and Ichikawa, N and Demetris, AJ and Starzl, TE and Murase, N (2002) Early passenger leukocyte migration and acute immune reactions in the rat recipient spleen during liver engraftment: With particular emphasis on donor major histocompatibility complex class II<sup>+</sup> cells. Transplantation, 74 (1). 103 - 111. ISSN 0041-1337

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Abstract

After a short course of tacrolimus, Lewis rat liver allografts induce donor-specific nonreactivity in Brown Norway recipients that is immunosuppression-independent after 28 days. To clarify the role of donor major histocompatibility complex (MHC) class II+ cells, we investigated the migration to the recipient splenic T- and B-cell compartments of different subsets of Lewis MHC class II+ passenger leukocytes. The rise and decline of immune activation were monitored in the hepatic allograft and in the host spleen by analyses of BrdU+ (proliferating) leukocytes, TUNEL+ (apoptotic) cells, apoptosis-associated molecules, TH1/TH2 cytokine profiles, and histoimmunocytochemical examination of graft and splenic tissues. Serial flow cytometry studies during the 28-day period of drug-assisted "hepatic tolerogenesis" showed that migratory MHC class II+ cells accounted for less than half of the donor cells in the host spleen. The class II+ cells consisted mostly of B cells that homed to splenic B-cell follicles with only a sparse representation of dendritic cells that were exclusively found in the splenic periarteriolar lymphoid sheath. In parallel studies, transplantation of the less tolerogenic heart produced a diminutive version of the same events, but with far fewer donor cells in the host spleen, evidence of sustained immune activation, and the development of chronic rejection by 100 days. The data are consistent with the paradigm that migration of donor leukocytes is the prime determinant of variable tolerance induction induced by transplantation of the liver and other organs, but without regard for donor MHC class II+ expression.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Okuda, T
Ishikawa, T
Azhipa, O
Ichikawa, N
Demetris, AJ
Starzl, TEtes11@pitt.eduTES11
Murase, N
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 15 July 2002
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 74
Number: 1
Page Range: 103 - 111
DOI or Unique Handle: 10.1097/00007890-200207150-00018
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062120773, Starzl CV No. 2171
Date Deposited: 08 Apr 2010 17:37
Last Modified: 13 Jun 2021 02:55
URI: http://d-scholarship.pitt.edu/id/eprint/5557

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