Summary

* Transplantation of tissues from one individual to a genetically nonidentical recipient leads to a specific immune response called rejection that can destroy the graft. The major molecular targets in allograft rejection are allogeneic class I and class II MHC molecules.

* Allogeneic MHC molecules may be presented on donor APCs to recipient T cells (the direct pathway), or the alloantigens may be picked up by host APCs that enter the graft or reside in draining lymphoid organs and be processed and presented to T cells as peptides associated with self MHC molecules (the indirect pathway).

* The frequency of T cells capable of recognizing allogeneic MHC molecules is very high, explaining why the response to alloantigens is much stronger than the response to conventional foreign antigens. The reasons for this high frequency are an inherent bias of T cells to recognize MHC molecules and because many different T cell clones specific for different foreign peptides plus self MHC molecules may cross-react with an individual allogeneic MHC molecule.

* Graft rejection is mediated by T cells, including CTLs that kill graft cells and helper T cells that cause cytokine-mediated inflammation resembling DTH reactions, and by antibodies.

* Several effector mechanisms cause rejection of solid organ grafts, and each mechanism may lead to a histologically characteristic reaction. Preexisting antibodies cause hyperacute rejection characterized by thrombosis of graft vessels. Alloreactive T cells and antibodies produced in response to the graft cause blood vessel wall damage and paren-chymal cell death, called acute rejection. Chronic rejection is characterized by fibrosis and vascular abnormalities (graft vasculopathy), which may clinical questions. American Journal of Transplantation 10:1135-1142, 2010.

Colvin RB, and RN Smith. Antibody-mediated organ-allograft rejection. Nature Review Immunology 5:807-817, 2005.

Heeger PS. T-cell allorecognition and transplant rejection: a summary and update. American Journal of Transplantation 3:525-533, 2003.

LaRosa DF, AH Rahman, and LA Turka. The innate immune system in allograft rejection and tolerance. Journal of Immunology 178:7503-7509, 2007.

Li XC, DM Rothstein, and MH Sayegh. Costimulatory pathways in transplantation: challenges and new developments. Immunological Reviews 229:271-293, 2009.

Clinical Transplantation

Chinen J, and RH Buckley. Transplantation immunology: solid organ and bone marrow. Journal of Allergy and Clinical Immunology 125:S324-S335, 2010.

Lechler RI, M Sykes, AW Thomson, and LA Turka. Organ transplantation—how much of the promise has been realized? Nature Medicine 11:605-613, 2005.

Ricordi C, and TB Strom. Clinical islet transplantation: advances and immunological challenges. Nature Reviews Immunology 4:259-268, 2004.

Rogers NJ, and RI Lechler. Allorecognition. American Journal of Transplantation 1:97-102, 2001.

Immunosuppression and Tolerance Induction to Allografts

Chidgey AP, D Layton, A Trounson, and RL Boyd. Tolerance strategies for stem-cell-based therapies. Nature 453:330-377, 2008.

Gibbons C, and M Sykes. Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed hematopoietic chimerism. Immunological Reviews 223: 334-360, 2008.

Halloran PF. Immunosuppressive drugs for kidney transplantation. New England Journal of Medicine 351:2715-2729, 2004.

Newell KA, CP Larsen, and AD Kirk. Transplant tolerance: converging on a moving target. Transplantation 81:1-6, 2006.

Safinia N, P Sagoo, R Lechler, and G Lombardi. Adoptive regulatory T cell therapy: challenges in clinical transplantation. Current Opinions in Organ Transplantation 15:427-434, 2010.

Turka LA, and RI Lechler. Towards the identification of bio-markers of transplantation tolerance. Nature Reviews Immunology 9:521-526, 2009.

Xenotransplantation

Yang YG, and M Sykes. Xenotransplantation: current status and a perspective on the future. Nature Reviews Immunology 7:519-531, 2007.

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