TGFbeta neutralization within cardiac allografts by decorin gene transfer attenuates chronic rejection.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Susan M FaustD Keith Bishop

Abstract

Chronic allograft rejection (CR) is the leading cause of late graft failure following organ transplantation. CR is a progressive disease, characterized by deteriorating graft function, interstitial fibrosis, cardiac hypertrophy, and occlusive neointima development. TGFbeta, known for its immunosuppressive qualities, plays a beneficial role in the transplant setting by maintaining alloreactive T cells in a hyporesponsive state, but has also been implicated in promoting graft fibrosis and CR. In the mouse vascularized cardiac allograft model, transient depletion of CD4(+) cells promotes graft survival but leads to CR, which is associated with intragraft TGFbeta expression. Decorin, an extracellular matrix protein, inhibits both TGFbeta bioactivity and gene expression. In this study, gene transfer of decorin into cardiac allografts was used to assess the impact of intragraft TGFbeta neutralization on CR, systemic donor-reactive T cell responses, and allograft acceptance. Decorin gene transfer and neutralization of TGFbeta in cardiac allografts significantly attenuated interstitial fibrosis, cardiac hypertrophy, and improved graft function, but did not result in systemic donor-reactive T cell responses. Thus, donor-reactive T and B...Continue Reading

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Citations

Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Tero A H Järvinen, Erkki Ruoslahti
Oct 23, 2013·Transplantation Research·Stefan M BrunnerStefan Fichtner-Feigl
Jul 12, 2014·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Simon A JonesGareth W Jones
Nov 24, 2018·Free Radical Research·Thu Thi VuJin Han
Apr 2, 2011·The Journal of Biological Chemistry·Cecilia VialEnrique Brandan
Mar 8, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·G SchiechlS Fichtner-Feigl

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