Biomarkers of transplantation tolerance: more hopeful than helpful?

Frontiers in Immunology
Stephen P CobboldHerman Waldmann

Abstract

A major limitation to the translation of tolerogenic therapies to clinical transplantation is a lack of biomarkers that can be used as surrogate measures for predicting the successful induction of immune tolerance which would allow for the safe withdrawal of immunosuppression. We have used three different mouse models of donor specific tolerance to skin grafts together with quantitative RT-PCR to search for potential biomarkers of tolerance using criteria based on the presence or activity of regulatory T cells and antigen presenting cells (APCs) within grafts or lymphoid organs. We find that significant differences in gene expression between tolerated and rejecting grafts are observed primarily within the grafted skin and not systemically or in the draining lymph node. The pattern of gene expression within long-term surviving tolerated grafts appear very similar to syngeneic grafts, with both having low levels of T cell and APC infiltration and a bias toward relative over-expression of "regulatory-associated" genes, while allografts destined for rejection show an overall increase in both "regulatory" and "effector" cell associated transcripts. We also, however, find an increase in a large number of regulatory genes, of both inn...Continue Reading

Citations

Oct 5, 2011·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A S Chong, R Sciammas
Mar 23, 2013·Transplant International : Official Journal of the European Society for Organ Transplantation·Deepak ChandrasekharanKathryn J Wood
Aug 21, 2013·Immunology·Stephen P Cobbold
Jun 20, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Dong-Gyun LimSong-Cheol Kim
Sep 16, 2014·Frontiers in Immunology·Duncan HowieStephen Cobbold
Apr 3, 2014·The Journal of Clinical Investigation·Herman WaldmannStephen Cobbold
Mar 19, 2019·Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation·Anna K NowocinWilson Wong

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Methods Mentioned

BETA
biopsies
Assay
transgenic

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