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Review
. 2012 Dec;39(6):629-42.
doi: 10.1053/j.seminoncol.2012.10.001.

Immune tolerance and transplantation

Onder Alpdogan  1 , Marcel R M van den Brink
Affiliations
Review

Immune tolerance and transplantation

Onder Alpdogan et al. Semin Oncol. 2012 Dec.

Abstract

Successful allogeneic hematopoietic stem cell transplantation (HSCT) and solid organ transplantation require development of a degree of immune tolerance against allogeneic antigens. T lymphocytes play a critical role in allograft rejection, graft failure, and graft-versus-host disease (GVHD). T-cell tolerance occurs by two different mechanisms: (1) depletion of self-reactive T cells during their maturation in the thymus (central tolerance), and (2) suppression/elimination of self-reactive mature T cells in the periphery (peripheral tolerance). Induction of transplant tolerance improves transplantation outcomes. Adoptive immunotherapy with immune suppressor cells including regulatory T cells, natural killer (NK)-T cells, veto cells, and facilitating cells are promising therapies for modulation of immune tolerance. Achieving mixed chimerism with the combination of thymic irradiation and T-cell-depleting antibodies, costimulatory molecule blockade with/without inhibitory signal activation, and elimination of alloreactive T cells with varying methods including pre- or post-transplant cyclophosphamide administration appear to be effective in inducing transplant tolerance.

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Figures

Figure 1
Figure 1
Thymopoiesis; T cell development in the thymus includes negative and positive selection of thymocytes. DN; double negative thymocytes, TEC; thymic epithelial cells, cTEC; cortical TEC, mTEC; medullary TEC, DC; dendritic cells, DP; double positive thymocytes, RAG; recombination activating genes, TCR; T cell receptor.
Figure 2
Figure 2
T Cell-APC interaction with costimulatory molecules. CTLA-4; Cytotoxic T- Lymphocyte Antigen 4, TCR; T cell receptor, MHC; Major histocompatibility molecules, ICOS; Inducible T-cell costimulator, PD-1; Programmed death-1, PD1-L; Programmed death-1 ligand.
Figure 3
Figure 3
Main mechanisms of T regulatory cell function. Treg suppress effector T cell function through cell contact (Figure 3A) and inhibitory cytokine and granzyme secretion (Figure 3B). T Eff; effector T cells, IDO; indoleamine 2,3-dioxygenase, Trp; Tryptophan, Kyn; kynurenines, IFNs; interferons
See this image and copyright information in PMC

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