Donor IL-4-treatment induces alternatively activated liver macrophages and IDO-expressing NK cells and promotes rat liver allograft acceptance

Transplant Immunology
Chuanmin WangG Alex Bishop

Abstract

Most approaches to transplant tolerance involve treatment of the recipient to prevent rejection. This study investigates donor treatment with IL-4 for its effect on subsequent rat liver allograft survival. Rat orthotopic liver transplants were performed in rejecting (PVG donor to Lewis recipient) or spontaneously tolerant (PVG to DA) strain combinations. Donors were untreated or injected intraperitoneally with IL-4 (30,000U/day) for 5days. Tissue infiltrates and gene expression were examined by immunohistochemistry and real-time quantitative PCR. IL-4 induced a marked leukocyte infiltrate in donor livers prior to transplant. Macrophages comprised the major population, although B cells, T cells and natural killer (NK) cells also increased. IL-4-induced liver macrophages had an alternatively activated phenotype with increased expression of mannose receptor but not inducible nitric oxide synthase (NOS2). IL-4 also induced IDO and IFN-gamma expression by NK cells. Donor IL-4-treatment converted rejection to acceptance in the majority of Lewis recipients (median survival time >96days) and did not prevent acceptance in DA recipients. Acceptance in Lewis recipients was associated with increased donor cell migration to recipient spleen...Continue Reading

References

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Citations

Sep 22, 2016·Clinical and Molecular Allergy : CMA·Marie-Pierre PiccinniSergio Romagnani
Nov 23, 2011·Molecular Medicine·Fernando Souza-Fonseca-GuimaraesJean-Marc Cavaillon
Aug 24, 2012·Transplantation·William van der TouwJonathan S Bromberg
Mar 20, 2020·Expert Review of Vaccines·Victor Ivanovich Seledtsov, Alexei A von Delwig
Sep 11, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tina L SumpterChandrashekhar R Gandhi
Mar 10, 2019·HPB : the Official Journal of the International Hepato Pancreato Biliary Association·Benjamin M StutchfieldStephen J Wigmore

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