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Towards the identification of biomarkers of transplantation tolerance

Nature Reviews Immunology volume 9, pages 521–526 (2009)Cite this article

Abstract

Although transplantation has been a standard medical practice for decades, the marked morbidity from the use of immunosuppressive drugs and poor long-term graft survival remain important limitations in the field. Achieving tolerance to transplanted organs should solve both problems, but has been an elusive goal. Recent advances in the human immunological toolbox have rekindled interest in studying the small number of transplant recipients who become tolerant to their grafts over time. The development of biomarkers of transplantation tolerance holds promise to improve the care of organ allograft recipients, to provide surrogate end points of tolerance induction strategies and to advance our understanding of the human immune response to both self and foreign antigens.

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Figure 1: Immune response to transplanted organs and tissues.
Figure 2: Towards the identification of biomarkers of transplantation.

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Acknowledgements

Research in the authors' laboratories is supported in part by the European Union (R.I.L.) and by National Institutes of Health, USA, grants AI-37691 and AI-41521 (L.A.T.). We thank A. Asare, J. Bluestone, M. Goldman, M. Hernandez-Fuentes, K. Newell and V. Seyfert-Margolis, as well as other colleagues that are too numerous to mention, for many helpful discussions.

Author information

Authors and Affiliations

  1. Laurence A. Turka is at the Department of Medicine, University of Pennsylvania, 111 Clinical Research Building 415 Curie Boulevard, Philadelphia 19104, USA, and the Immune Tolerance Network, Bethesda, Maryland, USA.,

    Laurence A. Turka

  2. Robert I. Lechler is at the Guy's, King's and St Thomas' Medical School, King's College, London SE1 9R7, UK.,

    Robert I. Lechler

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  2. Robert I. Lechler
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Correspondence to Laurence A. Turka.

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FURTHER INFORMATION

Laurence A. Turka's homepage

United States Renal Data System, 2008 Annual Data Report

Immune Tolerance Network

Glossary

γδ T cells

T cells that express the γδ T cell receptor (TCR). These T cells are mainly present in the skin, vagina and intestinal epithelium as intraepithelial lymphocytes. Although the exact function of γδ T cells is unknown, it has been suggested that mucosal γδ T cells are involved in innate immune responses.

Cyclosporin A

An immunosuppressive drug that inhibits calcineurin, a Ca2+-dependent serine/threonine phosphatase that is necessary for the nuclear translocation of the transcription factor NFAT (nuclear factor of activated T cells). It is used to prevent the rejection of transplanted organs and to treat some inflammatory diseases.

Full chimerism

A state in which essentially all haematopoietic elements are derived from a donor stem cell inoculum.

Immune-privileged site

An area in the body with a decreased immune response to foreign antigens, including tissue grafts. Traditionally, these sites include the brain, eye, testis and uterus.

Kupffer cell

A large, stellate- or pyramidal-shaped specialized macrophage that lines the sinusoidal vessels of the liver. Kupffer cells regulate local immune responses and remove microbial particles, endotoxin and other noxious substances that penetrate the portal venous system.

Mixed chimerism

A state of coexistence of host and allogeneic donor haematopoietic cells.

Mixed lymphocyte reaction

A tissue culture technique used for testing T cell reactivity. The proliferation of one population of T cells, induced by exposure to inactivated MHC-mismatched stimulator cells, is determined, for example, by measuring the incorporation of 3H thymidine into the DNA of dividing cells.

NKT cells

A subpopulation of T cells that expresses both natural killer (NK) cell and T cell markers. In the C57BL/6 mouse strain, NKT cells express the NK1.1 (NKRP1C) molecule and the αβTCR. Some NKT cells recognize CD1d-associated lipid antigens and express a restricted repertoire of TCRs.

Positive selection

A process that leads to the survival of immature thymocytes that express a TCR that binds with an appropriate affinity to self MHC molecules.

Regulatory T cell

A specialized type of T cell that can suppress the responses of other T cells. Regulatory T cells provide a crucial mechanism for the maintenance of peripheral self tolerance, and a subset of these cells is characterized by the expression of CD25 and the transcription factor forkhead box P3.

Transforming growth factor-β

(TGFβ). A pleiotropic anti-inflammatory cytokine that is produced by activated T cells and mononuclear phagocytes as well as other cell types. The effects of TGFβ are mainly anti-proliferative. It antagonizes the actions of pro-inflammatory cytokines by inhibiting both macrophage activation and T cell proliferation and differentiation.

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Turka, L., Lechler, R. Towards the identification of biomarkers of transplantation tolerance. Nat Rev Immunol 9, 521–526 (2009). https://doi.org/10.1038/nri2568

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