Hepatic infiltrates in operational tolerant XXXX after liver transplantation show enrichment of regulatory T cells before proinflammatory genes are down-regulated.

@entity1 @entity404 @entity1200 @entity403 @entity1575
UNASSIGNED: Immunosuppression can be discontinued from selected and stable @entity1 after liver transplantation resulting in spontaneous operational tolerance (SOT), although the underlying mechanisms remain elusive. Thus we analyzed serial liver biopsies from adult liver recipients enrolled in a prospective multi-center immunosuppression withdrawal trial employing immunophenotyping and transcriptional profiling. Liver samples were collected before the initiation of weaning, at time of rejection, or 1 and 3 years after complete drug discontinuation. Unexpectedly the tolerated grafts developed portal tract expansion with increased T cell infiltration after immunosuppression withdrawal. This was associated with transient and preferential accumulation of @entity404 (+) @entity403 (+) cells and a trend towards up-regulation of immune activation and regulatory genes, without signs of rejection. At the same time no markers of endothelial damage or activation were noted. Portal infiltrates persisted at 3 year, but were characterized by decreased expression of genes associated with @entity1200 . Furthermore SOT was not associated with a progressive @entity1575 up to five years. These data suggest that SOT involves several mechanisms: a long-lasting local immune cell persistence with a transient regulatory T cells accumulation followed by a down-regulation of immune activated genes over years. These results have important implications for designs and follow-up of weaning trials. This article is protected by copyright. All rights reserved.
