Lymphocyte apoptosis and cell replacement in human liver allografts

Clouston, Andrew D., Jonsson, Julie R., Balderson, Glenda A., Fawcett, Jonathon, Lynch, Stephen V., Kelso, Anne and Powell, Elizabeth E. (2002) Lymphocyte apoptosis and cell replacement in human liver allografts. Transplantation, 73 11: 1828-1834. doi:10.1097/00007890-200206150-00022

Author Clouston, Andrew D.
Jonsson, Julie R.
Balderson, Glenda A.
Fawcett, Jonathon
Lynch, Stephen V.
Kelso, Anne
Powell, Elizabeth E.
Title Lymphocyte apoptosis and cell replacement in human liver allografts
Journal name Transplantation   Check publisher's open access policy
ISSN 0041-1337
Publication date 2002-06-15
Sub-type Article (original research)
DOI 10.1097/00007890-200206150-00022
Volume 73
Issue 11
Start page 1828
End page 1834
Total pages 7
Editor A. P. Monaco
Place of publication Baltimore
Publisher Lippincott Williams & Wilkins
Language eng
Subject C1
730109 Surgical methods and procedures
110323 Surgery
Formatted abstract
Background. Apoptosis of graft-infiltrating T cells has been described after rodent liver transplantation. The aim of this study was to assess lymphocyte apoptosis in human allografts. Additionally, kinetics of leukocyte turnover were studied to determine whether apoptotic cells were likely to be of donor or recipient origin.

Methods. Liver biopsy specimens (n=36) taken between days 3 and 1855 were stained with terminal deoxynucleotidyl transferase dUTP nick end-labeling and anti-CD3 to detect apoptotic lymphocytes. Renal allograft and hepatitis C biopsy specimens served as controls. Donor cell turnover was studied in sex-mismatched grafts using Y-chromosome in situ hybridization to detect recipient cells and double immunostaining for leukocyte phenotyping.

Results. T-cell apoptosis was prominent in hepatic sinusoids (72% of biopsy specimens) as early as day 3. It ranged from 0% to 18.2% of CD3+ cells (mean 5.28+/-0.82%) and persisted for >14 days, including time points >1 year. There was no difference between biopsy specimens with or without rejection (6.34+/-1.14% and 4.61+/-1.13%, P =NS). Apoptotic cells in portal tracts were less frequent (33% of biopsy specimens) and less abundant (1.13+/-0.36%, P <0.0001). No lymphocyte apoptosis was seen in renal allograft biopsy specimens or hepatitis C biopsy specimens, indicating that it is a distinctive feature of the liver allograft. Persisting lymphocyte apoptosis even after donor lymphocytes had been replaced suggests that recipient lymphocyte deletion must occur. Donor Kupffer cells persisted for many months.

Conclusions. Our results suggest that the sinusoidal microenvironment promotes recipient lymphocyte apoptosis, which may account for the improved outcome of liver grafts compared with other organ allografts.

(C) 2002 Lippincott Williams & Wilkins, Inc.
Keyword Immunology
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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Created: Wed, 15 Aug 2007, 04:42:00 EST