Graft Rejection: Immunological Suppression

Abstract

Transplantation of solid organs is the treatment of choice for most patients with end‐stage organ diseases. In the absence of pharmacological immunosuppression, recognition of foreign (allogeneic) histocompatibility proteins expressed on donor cells by the recipient's immune system results in rejection of the transplanted tissue(s). One‐year renal transplant survival is now routinely over 90% in most centres, largely the result of improvements in immunosuppressive drugs. In this article, we review commonly used immunosuppressive medications and discuss their pharmacological modes of action. Given that the long‐term graft outcomes remain poor, despite improvements in early transplant survival, we discuss, in addition, novel experimental strategies for the induction of tolerance to transplanted tissues that have translational relevance to human organ recipients.

Key Concepts

  • The major limitation of solid organ transplantation is long‐term immunosuppression, which either results in excessive mortality and morbidity or is insufficient to prevent chronic rejection of transplanted tissues.
  • An understanding of transplant rejection and pharmacological targets of immunosuppression is a key to devising novel strategies of preventing rejection by inducing transplant tolerance.

Keywords: transplantation; rejection; tissue typing; immunosuppression

Figure 1. Outline map of genes coding for human leucocyte antigen (HLA) molecules on the short arm of chromosome 6.
Figure 2. Transplant survival rate in recipients mismatched for donor human leucocyte antigen (HLA) A, HLA‐B and HLA‐DR. Reproduced from Morris et al., 1999 © Elsevier.
Figure 3. Stages of the cell cycle.
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Further Reading

Barnett ANR , Hadjianastassiou VG and Mamode N (2013) Rituximab in renal transplantation. Transplant International 26 (6): 563–575.

Becker LE , Susal C and Morath C (2013) Kidney transplantation across HLA and ABO antibody barriers. Current Opinion in Organ Transplantation 18 (4): 445–454.

Ginns LC , Cosimi AB and Morris PJ (eds) (1999) Transplantation. Oxford, UK: Blackwell Science.

The Anthony Nolan Bone Marrow Trust Website (2000) The Anthony Nolan Bone Marrow Trust. http://www.anthonynolan.com

The Eurotransplant International Foundation (2000) Eurotransplant. http://www.eurotransplant.nl

Thomson AW and Starzl TE (eds) (1994) Immunosuppressive Drugs. London: Edward Arnold.

United Network for Organ Sharing (2000) United Network for Organ Sharing Online. http://www.unos.org

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Afzali, Behdad, Lechler, Robert, and Lombardi, Giovanna(Jul 2015) Graft Rejection: Immunological Suppression. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001231.pub3]