Transplant tolerance: models, concepts and facts

Monk, N.J., Hargreaves, R.E.G., Simpson, E., Dyson, J.P. and Jurcevic, S. 2006. Transplant tolerance: models, concepts and facts. Journal of Molecular Medicine. 84 (4), pp. 295-304. https://doi.org/10.1007/s00109-005-0006-4

TitleTransplant tolerance: models, concepts and facts
TypeJournal article
AuthorsMonk, N.J., Hargreaves, R.E.G., Simpson, E., Dyson, J.P. and Jurcevic, S.
Abstract

Despite extensive research, our understanding of immunological tolerance to self-antigens is incomplete, and the goal of achieving tolerance to allogeneic transplanted tissue remains elusive. Currently, it is generally believed that the blockade of T cell co-stimulation offers considerable potential for achieving tolerance in the clinical setting. However, the recent finding that CD154-specific antibody may act through the depletion of activated T cells rather than co-stimulation blockade alone highlights the need for a re-evaluation of published data and the role of co-stimulation blockade in transplant tolerance. Activated T cells are programmed to die unless they receive sufficient survival signals in the form of inflammatory and lymphotropic cytokines produced by activated antigen-presenting cells or the T cells themselves. In conditions where the threshold for surviving activation is not reached, for example when a small number of responder T cells are activated in the absence of substantial injury or inflammation, the ensuing death of all activated T cells can result in deletional tolerance. Therefore, we propose that tolerance represents a failure of T cells to survive activation and develop into memory cells. This concept is likely to apply in the transplant setting, where the strength of the alloresponse depends on both the number/phenotype of the recipients' alloreactive T cells and immunogenicity of the transplanted tissue. Hence, in some rodent donor-recipient strain combinations that instigate a weak alloresponse, many treatments that only modestly decrease the alloresponse can achieve tolerance. In contrast, clinical transplantation is characterised by a strong alloresponse and highly immunogenic allografts, and thus, most treatments fail to control allograft rejection, and tolerance is difficult to achieve.

JournalJournal of Molecular Medicine
Journal citation84 (4), pp. 295-304
ISSN1432-1440
0946-2716
Year2006
PublisherSpringer
Digital Object Identifier (DOI)https://doi.org/10.1007/s00109-005-0006-4
PubMed ID16501935
Publication dates
Published25 Feb 2006

Related outputs

The role of Inflammation in platelet activation (and in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis)
Rashvand, S., Dishkelov, A. and Jurcevic, S. 2024. The role of Inflammation in platelet activation (and in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis). GTH Congress 2024 – 68th Annual Meeting of the Society of Thrombosis and Haemostasis Research – Building Bridges in Coagulation. Vienna, Austria 27 Feb - 01 Mar 2024 Georg Thieme Verlag. https://doi.org/10.1055/s-0044-1779178

microRNA-21 Regulates Stemness in Pancreatic Ductal Adenocarcinoma Cells
Mortoglou, M., Miralles, F., Arisan, E.D., Dart, A., Jurcevic, S., Lange, S. and Uysal Onganer, P. 2022. microRNA-21 Regulates Stemness in Pancreatic Ductal Adenocarcinoma Cells. International Journal of Molecular Sciences. 23 (3) 1275. https://doi.org/10.3390/ijms23031275

Epitope recognition of peptide-imprinted polymers for Regenerating protein 1 (REG1)
Lee, M.H., Thomas, J.L., Liao, C.L., Jurcevic, S., Crnogorac-Jurcevic, T. and Lin, H.Y. 2018. Epitope recognition of peptide-imprinted polymers for Regenerating protein 1 (REG1). Separation and Purification Technology. 192, pp. 213-219. https://doi.org/10.1016/j.seppur.2017.09.071

Polymers imprinted with three REG1B peptides for electrochemical determination of Regenerating Protein 1B, a urinary biomarker for pancreatic ductal adenocarcinoma
Jurcevic, S., Lee, M-H., Thomas, J.L., Liao, C-L., Crnogorac-Jurcevic, T. and Lin, H-Y. 2017. Polymers imprinted with three REG1B peptides for electrochemical determination of Regenerating Protein 1B, a urinary biomarker for pancreatic ductal adenocarcinoma. Microchimica Acta. 184 (6), p. 1773–1780. https://doi.org/10.1007/s00604-017-2169-4

PRT062607 Achieves Complete Inhibition of the Spleen Tyrosine Kinase at Tolerated Exposures Following Oral Dosing in Healthy Volunteers
Coffey, G., Rani, A., Betz, A., Pak, Y., Haberstock-Debic, H., Pandey, A., Hollenbach, S., Gretler, D.D., Mant, T., Jurcevic, S. and Simha, U. 2017. PRT062607 Achieves Complete Inhibition of the Spleen Tyrosine Kinase at Tolerated Exposures Following Oral Dosing in Healthy Volunteers. Journal of Clinical Pharmacology. 57 (2), pp. 194-210. https://doi.org/10.1002/jcph.794

Effects of multiple-dose ponesimod, a selective SIP1 receptor modulator, on lymphocyte subsets in healthy humans
Jurcevic, S., Juif, P.E., Hamid, C., Greenlaw, R., D'Ambrosio, D. and Dingemanse, J. 2016. Effects of multiple-dose ponesimod, a selective SIP1 receptor modulator, on lymphocyte subsets in healthy humans. Drug Design, Development and Therapy. 11, pp. 123-131. https://doi.org/10.2147/DDDT.S120399

The effect of a selective CXCR2 antagonist (AZD5069) on human blood neutrophil count and innate immune functions.
Jurcevic, S., Humfrey, C., Uddin, M., Warrington, S., Larsson, B. and Keen, C. 2015. The effect of a selective CXCR2 antagonist (AZD5069) on human blood neutrophil count and innate immune functions. Br J Clin Pharmacol. . 80 (6), pp. 1324-36. https://doi.org/10.1111/bcp.12724

The effect of prasugrel on ADP-stimulated markers of platelet activation in patients with sickle cell disease.
Jakubowski, J.A., Zhou, C., Winters, K.J., Lachno, D.R., Howard, J., Payne, C.D., Mant, T., Jurcevic, S. and Frelinger, A.L. 2015. The effect of prasugrel on ADP-stimulated markers of platelet activation in patients with sickle cell disease. Platelets. 26 (5), pp. 474-479. https://doi.org/10.3109/09537104.2014.940887

FRA2 is a STAT5 target gene regulated by IL-2 in human CD4 T cells
Rani, A., Greenlaw, R., Runglall, M., Jurcevic, S. and John, S. 2014. FRA2 is a STAT5 target gene regulated by IL-2 in human CD4 T cells. PLoS ONE. 9 (2), p. e90370. https://doi.org/10.1371/journal.pone.0090370

A phase 1 study of prasugrel in patients with sickle cell disease: effects on biomarkers of platelet activation and coagulation
Jakubowski, J.A., Zhou, C., Jurcevic, S., Winters, K.J., Lachno, D.R., Frelinger, A.L., Gupta, N., Howard, J., Payne, C.D. and Mant, T. 2014. A phase 1 study of prasugrel in patients with sickle cell disease: effects on biomarkers of platelet activation and coagulation. Thrombosis Research. 133 (2), pp. 190-5. https://doi.org/10.1016/j.thromres.2013.12.008

Antibody combination therapy targeting CD25, CD70 and CD8 reduces islet inflammation and improves glycaemia in diabetic mice
Alkhamis, T., Barbic, J., Crnogorac-Jurcevic, T., Greenlaw, R.E., Peakman, M. and Jurcevic, S. 2012. Antibody combination therapy targeting CD25, CD70 and CD8 reduces islet inflammation and improves glycaemia in diabetic mice. Clinical & Experimental Immunology. 170 (2), p. 139–148 PMC3482360. https://doi.org/10.1111/j.1365-2249.2012.04651.x

The Role of the Fc Region in CD70-specific Antibody Effects on Cardiac Transplant Survival
Jurcevic, S., Shariff, H., Greenlaw, R.E., Meader, L., Gardner, N., Yagita, H., Coccia, M. and Mamode, N. 2011. The Role of the Fc Region in CD70-specific Antibody Effects on Cardiac Transplant Survival. Transplantation. 92 (11), pp. 1194-1201. https://doi.org/10.1097/TP.0b013e3182347ecd

An Antibody Combination That Targets Activated T Cells Extends Graft Survival in Sensitized Recipients
Jurcevic, S. 2008. An Antibody Combination That Targets Activated T Cells Extends Graft Survival in Sensitized Recipients. American Journal of Transplantation. 8 (11), pp. 2272-2282. https://doi.org/10.1111/j.1600-6143.2008.02393.x

R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation
Jurcevic, S., Braselmann, S., Taylor, V., Zhao, H., Wang, S. and Masuda, E.S. 2006. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. Journal of Pharmacology and Experimental Therapeutics. 319 (3), pp. 998-1008 109058/3152109. https://doi.org/10.1124/jpet.106.109058

Selective depletion of activated T cells: the CD40L-specific antibody experience
Hargreaves, R.E.G., Monk, N.J. and Jurcevic, S. 2004. Selective depletion of activated T cells: the CD40L-specific antibody experience. TRENDS in Molecular Medicine. 10 (3), pp. 130-135. https://doi.org/10.1016/j.molmed.2004.01.009

Fc-dependent depletion of activated T cells occurs through CD40L-specific antibody rather than costimulation blockade
Monk, N.J., Hargreaves, R.E.G., Marsh, J.E., Farrar, C.A., Sacks, S.H., Millrain, M., Simpson, E., Dyson, J. and Jurcevic, S. 2003. Fc-dependent depletion of activated T cells occurs through CD40L-specific antibody rather than costimulation blockade. Nature Medicine. 9 (10), pp. 1275-1280. https://doi.org/10.1038/nm931

Permalink - https://westminsterresearch.westminster.ac.uk/item/w5z99/transplant-tolerance-models-concepts-and-facts


Share this

Usage statistics

63 total views
0 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.