Immunological tolerance-related genes in a spontaneous tolerant model of rat liver transplantation explored by suppression subtractive hybridization.

Abstract:

:Natural immunological tolerance can be induced in certain types of allogeneic liver transplantation in rats. To screen for genes associated with the induction of tolerance, suppression subtractive hybridization was performed in the rat liver transplantation model between a DA donor and PVG recipient combination where spontaneous immunological tolerance is known to occur without any immunosuppressive treatment. As a result, 112 genes were cloned from a DA liver graft that survived for 20 days in the fully allogeneic PVG recipient. After confirmation of the expression intensity using an in-house manufactured DNA array with cDNAs from the DA graft, 36 genes were classified in the highly expressed group and 26 moderately expressed group. In the first group, there were 8 immunoglobulin-related genes and 6 MHC class II-related genes, suggesting the existence of an underlying rejection response. Among those genes, an antiapoptotic gene in the p38 MAP kinase pathway, heme oxygenase gene (HO-1), and a ras cascade gene, IQ motif containing GTPase activating protein 1 (Iqgapl), retained biological significance. The results suggested that the molecular response to a liver graft tends to be antiapoptotic and to terminate the rejection response. Unfortunately, there was no gene identified that qualified as a putative immunosuppressive protein, liver suppressor factor-1 (LSF-1). The panel of genes identified in the present work will be a useful panel of candidate genes to investigate the induction of spontaneous tolerance.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Zhang H,Ohmi K,Hirasawa A,Enosawa S,Hara Y,Tamura A,Tsujimoto G

doi

10.3727/000000008783906955

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

195-201

issue

1-2

eissn

0963-6897

issn

1555-3892

journal_volume

17

pub_type

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