Transplant Tolerance: New Insights and Strategies for Long-Term Allograft Acceptance

One of the greatest advances in medicine during the past century is the introduction of organ transplantation. This therapeutic strategy designed to treat organ failure and organ dysfunction allows to prolong the survival of many patients that are faced with no other treatment option. Today, organ transplantation between genetically dissimilar individuals (allogeneic grafting) is a procedure widely used as a therapeutic alternative in cases of organ failure, hematological disease treatment, and some malignancies. Despite the potential of organ transplantation, the administration of immunosuppressive drugs required for allograft acceptance induces severe immunosuppression in transplanted patients, which leads to serious side effects such as infection with opportunistic pathogens and the occurrence of neoplasias, in addition to the known intrinsic toxicity of these drugs. To solve this setback in allotransplantation, researchers have focused on manipulating the immune response in order to create a state of tolerance rather than unspecific immunosuppression. Here, we describe the different treatments and some of the novel immunotherapeutic strategies undertaken to induce transplantation tolerance.

• Publication year

  2013

• Venue

  Clinical and Developmental Immunology

• Publication date

  2013-05-12

• Fields of study

  Medicine

• Identifiers
  DOI 10.1155/2013/210506PMID 23762087PMCID 3665173
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Mesenchymal stromal cells to promote solid organ transplantation tolerance

  2013cited by this paper
• IFN-γ-induced iNOS expression in mouse regulatory macrophages prolongs allograft survival in fully immunocompetent recipients.

  2013cited by this paper
• Prostaglandin E2 Potentiates Mesenchymal Stem Cell–Induced IL-10+IFN-γ+CD4+ Regulatory T Cells To Control Transplant Arteriosclerosis

  2013cited by this paper
• Overcoming Memory T‐Cell Responses for Induction of Delayed Tolerance in Nonhuman Primates

  2012cited by this paper
• The role of complement in the early immune response to transplantation

  2012cited by this paper
• Reviews on mysterious vascular endothelial cells in renal allografts

  2012cited by this paper
• Cyclosporine: A Review

  2012cited by this paper
• Regulatory immune cells in transplantation

  2012influential reference
• The Role of Coinhibitory Signaling Pathways in Transplantation and Tolerance

  2012cited by this paper
• Emerging concepts in haematopoietic cell transplantation

  2012cited by this paper
• A Novel Pathway of Chronic Allograft Rejection Mediated by NK Cells and Alloantibody

  2012cited by this paper
• Immuno-intervention for the induction of transplantation tolerance through mixed chimerism.

  2011cited by this paper
• Tolerogenic dendritic cells and their role in transplantation.

  2011cited by this paper
• The Novel Costimulatory Programmed Death Ligand 1/B7.1 Pathway Is Functional in Inhibiting Alloimmune Responses In Vivo

  2011cited by this paper
• Enhancement of Suboptimal CD8 Cytotoxic T Cell Effector Function In Vivo Using Antigen-Specific CD80 Defective T Cells

  2011cited by this paper
• Coexpression of Donor Peptide/Recipient MHC Complex and Intact Donor MHC: Evidence for a Link between the Direct and Indirect Pathways

  2011cited by this paper
• Exosomes and Cancer: A Newly Described Pathway of Immune Suppression

  2011cited by this paper
• Rapamycin-conditioned, alloantigen-pulsed myeloid dendritic cells present donor MHC class I/peptide via the semi-direct pathway and inhibit survival of antigen-specific CD8(+) T cells in vitro and in vivo.

  2011cited by this paper
• Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation

  2011cited by this paper
• Cutting Edge: Immunological Consequences and Trafficking of Human Regulatory Macrophages Administered to Renal Transplant Recipients

  2011cited by this paper
• The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells.

  2011cited by this paper
• Dendritic cells as a tool to induce transplantation tolerance: obstacles and opportunities.

  2011cited by this paper
• Control of central and peripheral tolerance by Aire

  2011cited by this paper
• Exosomes Released from M.tuberculosis Infected Cells Can Suppress IFN-γ Mediated Activation of Naïve Macrophages

  2011cited by this paper
• Delivery of alloantigens via apoptotic cells generates dendritic cells with an immature tolerogenic phenotype.

  2011cited by this paper
• Tolerogenic dendritic cells and their potential applications

  2011cited by this paper
• Therapeutic Efficacy of Polyclonal Tregs Does Not Require Rapamycin in a Low-Dose Irradiation Bone Marrow Transplantation Model

  2011cited by this paper
• Pattern recognition receptors and inflammation.

  2010cited by this paper
• The role of the thymus in tolerance.

  2010cited by this paper
• Dendritic cells and B cells cooperate in the generation of CD4(+)CD25(+)FOXP3(+) allogeneic T cells.

  2010cited by this paper
• Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

  2010cited by this paper
• Transplantation tolerance through mixed chimerism

  2010influential reference
• Mechanisms maintaining peripheral tolerance

  2010cited by this paper
• The Significance of Non–T-Cell Pathways in Graft Rejection: Implications for Transplant Tolerance

  2010cited by this paper
• Endogenous dendritic cells mediate the effects of intravenously injected therapeutic immunosuppressive dendritic cells in transplantation.

  2010cited by this paper
• Settling the thymus: immigration requirements

  2009cited by this paper
• BIOLOGICAL INCOMPATIBILITY IN KIDNEY TRANSPLANTATION IN DOGS

  2009cited by this paper
• Nonmyeloablative conditioning with total lymphoid irradiation and antithymocyte globulin: an update

  2009cited by this paper
• Infusion of Mesenchymal Stem Cells and Rapamycin Synergize to Attenuate Alloimmune Responses and Promote Cardiac Allograft Tolerance

  2009cited by this paper
• Antibody-mediated rejection: treatment alternatives and outcomes.

  2009cited by this paper
• Biological incompatibility in kidney transplantation in dogs. II. Serological investigations.

  2009cited by this paper
• Induction of allogeneic mixed chimerism by immature dendritic cells and bone marrow transplantation leads to prolonged tolerance to major histocompatibility complex disparate allografts

  2009cited by this paper
• Tolerance in renal transplantation: is mixed chimerism the missing link?

  2009cited by this paper
• Transforming growth factor-beta and all-trans retinoic acid generate ex vivo transgenic regulatory T cells with intestinal homing receptors.

  2009cited by this paper
• Mammalian Target of Rapamycin Inhibition and Alloantigen-Specific Regulatory T Cells Synergize To Promote Long-Term Graft Survival in Immunocompetent Recipients

  2009cited by this paper
• Maintenance of Peripheral Tolerance through Controlled Tissue Homing of Antigen-Specific T Cells in K14-mOVA Mice 1

  2009cited by this paper
• Thymus Exosomes-Like Particles Induce Regulatory T Cells1

  2008cited by this paper
• Macrophages Driven to a Novel State of Activation Have Anti-Inflammatory Properties in Mice1

  2008cited by this paper
• Apoptotic cells induce dendritic cell‐mediated suppression via interferon‐γ‐induced IDO

  2008cited by this paper
• Apoptotic Cells Induce Immunosuppression through Dendritic Cells: Critical Roles of IFN-γ and Nitric Oxide1

  2008cited by this paper
• Conferring indirect allospecificity on CD4+CD25+ Tregs by TCR gene transfer favors transplantation tolerance in mice.

  2008cited by this paper
• HLA-mismatched renal transplantation without maintenance immunosuppression.

  2008cited by this paper
• Clinical experience with mixed chimerism to induce transplantation tolerance

  2008influential reference
• Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes

  2008cited by this paper
• Apoptotic cells induce dendritic cell-mediated suppression via interferon-gamma-induced IDO.

  2008cited by this paper
• PD-1 and its ligands in tolerance and immunity.

  2008cited by this paper
• Apoptotic cells induce immunosuppression through dendritic cells: critical roles of IFN-gamma and nitric oxide.

  2008cited by this paper
• RNAi-mediated chromatin silencing in fission yeast.

  2008cited by this paper
• Macrophage Depletion Suppresses Cardiac Allograft Vasculopathy in Mice

  2007cited by this paper
• Rapamycin-Conditioned Dendritic Cells Are Poor Stimulators of Allogeneic CD4+ T Cells, but Enrich for Antigen-Specific Foxp3+ T Regulatory Cells and Promote Organ Transplant Tolerance1

  2007cited by this paper
• In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance.

  2007cited by this paper
• Generation of dendritic cells with regulatory properties.

  2007influential reference
• Allorecognition and the alloresponse: clinical implications.

  2007cited by this paper
• Tolerogenic dendritic cells and the quest for transplant tolerance

  2007cited by this paper
• Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

  2006cited by this paper
• Journey through the thymus: stromal guides for T-cell development and selection

  2006cited by this paper
• Monitoring the T-Cell Receptor Repertoire at Single-Clone Resolution

  2006cited by this paper
• The Immune Regulatory Effect of Apoptotic Cells and Exosomes on Dendritic Cells: Its Impact on Transplantation

  2006cited by this paper
• Tissue expression of PD-L1 mediates peripheral T cell tolerance

  2006cited by this paper
• The apoptotic cell receptor CR3, but not αvβ5, is a regulator of human dendritic cell immunostimulatory function

  2006cited by this paper
• Insulin-induced remission in new-onset NOD mice is maintained by the PD-1–PD-L1 pathway

  2006cited by this paper
• Use of the Inhibitory Effect of Apoptotic Cells on Dendritic Cells for Graft Survival Via T‐Cell Deletion and Regulatory T Cells

  2006cited by this paper
• “Alternatively Activated” Dendritic Cells Preferentially Secrete IL-10, Expand Foxp3+CD4+ T Cells, and Induce Long-Term Organ Allograft Survival in Combination with CTLA4-Ig1

  2006cited by this paper
• The apoptotic-cell receptor CR3, but not alphavbeta5, is a regulator of human dendritic-cell immunostimulatory function.

  2006cited by this paper
• Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus

  2006cited by this paper
• Induction of Tolerance across Fully Mismatched Barriers by a Nonmyeloablative Treatment excluding Antibodies or Irradiation Use

  2006cited by this paper
• Specific Recognition of Apoptotic Cells Reveals a Ubiquitous and Unconventional Innate Immunity*

  2006cited by this paper
• Induction of Tolerance by Exosomes and Short‐Term Immunosuppression in a Fully MHC‐Mismatched Rat Cardiac Allograft Model

  2006cited by this paper
• Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype.

  2005cited by this paper
• Regulatory T cells in transplantation tolerance.

  2005cited by this paper
• Exosomes Derived from IL-10-Treated Dendritic Cells Can Suppress Inflammation and Collagen-Induced Arthritis 1

  2005cited by this paper
• Autoimmune polyendocrinopathy syndrome type 1 (APS1) and AIRE gene: new views on molecular basis of autoimmunity.

  2005cited by this paper
• Development of Autoimmunity against Transcriptionally Unrepressed Target Antigen in the Thymus of Aire-Deficient Mice1

  2005cited by this paper
• ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming.

  2005cited by this paper
• Organ transplantation—how much of the promise has been realized?

  2005cited by this paper
• Irradiated Pancreatic Cancer Cells Undergo both Apoptosis and Necrosis, and Could Be Phagocytized by Dendritic Cells

  2005cited by this paper
• The release of microparticles by apoptotic cells and their effects on macrophages

  2005cited by this paper
• Dendritic Cells: Tools and Targets for Transplant Tolerance

  2005cited by this paper
• Apoptotic cells at the crossroads of tolerance and immunity.

  2005influential reference
• Marked Prolongation of Murine Cardiac Allograft Survival Using Recipient Immature Dendritic Cells Loaded with Donor‐Derived Apoptotic Cells

  2004cited by this paper
• Distinct Maturation of, but Not Migration between, Human Monocyte-Derived Dendritic Cells upon Ingestion of Apoptotic Cells of Early or Late Phases 1

  2004cited by this paper
• Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes.

  2004cited by this paper
• A Novel Pathway of Alloantigen Presentation by Dendritic Cells1

  2004cited by this paper
• Death-defying immunity: do apoptotic cells influence antigen processing and presentation?

  2004cited by this paper
• Induction of FOXP3‐expressing regulatory CD4pos T cells by human mature autologous dendritic cells

  2004cited by this paper
• CD154 Blockade for Induction of Mixed Chimerism and Prolonged Renal Allograft Survival in Nonhuman Primates

  2004cited by this paper
• Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection1

  2003cited by this paper
• Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity.

  2003cited by this paper
• Thymic selection revisited: how essential is it?

  2003cited by this paper
• Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production.

  2003cited by this paper

• Updates in tolerance: future directions to improve kidney allograft survival.

  2026cites this paper
• Resolving ScRNA-Seq Signatures of Antigen-Specific CD4+ T Cells in Tolerance across Semi-Allogeneic Transplantation and Pregnancy

  2025cites this paper
• Hematopoietic cell-based and non-hematopoietic cell-based strategies for immune tolerance induction in living-donor renal transplantation: A systematic review.

  2023cites this paper
• The fate of adipose tissue and adipose-derived stem cells in allograft

  2023influential citation
• CD4+CD25+ T regulatory cells in renal transplantation

  2022cites this paper
• FAS-670A>G gene polymorphism and the risk of allograft rejection after organ transplantation: a systematic review and meta-analysis

  2021cites this paper
• Application of PLGA nano/microparticle delivery systems for immunomodulation and prevention of allotransplant rejection

  2020cites this paper
• The human leukocyte antigen system in human disease and transplantation medicine

  2020cites this paper
• Human embryonic stem cells (hESC) as a source of insulin-producing cells

  2020cites this paper
• Management of abdominal wall defects – case series

  2020cites this paper
• SOME APPLICATIONS OF ALLO- AND XENOGRAFT MODELS FOR DEVELOPING NOVEL ANTI-CANCER VACCINES AND ONCOLYTIC VIRUSES

  2019cites this paper
• Adaptive features of innate immune cells and their relevance to graft rejection.

  2019cites this paper
• Mechanism Development of Accommodation and Tolerance in Transplant

  2019cites this paper
• Innate Immune Determinants of Graft-Versus-Host Disease and Bidirectional Immune Tolerance in Allogeneic Transplantation

  2019cites this paper
• Face Transplantation and Identity: Hidden Identities, Exceptions, and Exclusions

  2019cites this paper
• Bone vascularized composite allotransplantation model in swine tibial defect: Evaluation of surgical angiogenesis and transplant viability

  2019cites this paper
• Blimp‐1 prolongs allograft survival without regimen via influencing T cell development in favor of regulatory T cells while suppressing Th1

  2018cites this paper
• Messengers of tolerance.

  2018cites this paper
• Immunomodulatory plasticity of mesenchymal stem cells: a potential key to successful solid organ transplantation

  2018cites this paper
• Mesenchymal stem cells and their immunosuppressive role in transplantation tolerance

  2018cites this paper
• Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine

  2017cites this paper
• Six years' experience of tolerance induction in renal transplantation using stem cell therapy.

  2017cites this paper
• Transplantation of Bioprinted Tissues and Organs nges and Future Perspectives Technical and Clinical Challe

  2017cites this paper
• Stem cell therapy facilitates tolerance in renal transplantation

  2017cites this paper
• Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives

  2017cites this paper
• Flexible Macromolecule versus Rigid Particle Retention in the Injected Skin and Accumulation in Draining Lymph Nodes Are Differentially Influenced by Hydrodynamic Size.

  2017cites this paper
• Home-grown kidneys: challenges and mechanisms behind tissue engineering for the treatment of chronic kidney disease

  2017cites this paper
• Regulation of Alloreactive CD8 T Cell Responses by Costimulation and Inflammation

  2017cites this paper
• ROLE OF VASCULAR REMODELING IN THE ACCUMULATION, CLEARANCE, AND BIODISTRIBUTION OF BIOMOLECULAR FACTORS IN MELANOMA

  2017cites this paper
• Chemokines and transplant outcome.

  2016cites this paper
• The renal microenvironment modifies dendritic cell phenotype.

  2016cites this paper
• Athymic nude mice as an experimental model for cancer treatment.

  2016cites this paper
• Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

  2016cites this paper
• Genetic barriers in transplantation medicine

  2016cites this paper
• Engineering erythrocytes for the modulation of drugs' and contrasting agents' pharmacokinetics and biodistribution.

  2016cites this paper
• Soluble fibrinogen like protein 2 (sFGL2), the novel effector molecule for immunoregulation

  2016cites this paper
• Use of IVIg to identify potential miRNA targets for allograft rejection and GvHD therapy

  2015cites this paper
• Generation of suppressive blood cells for control of allograft rejection.

  2015cites this paper
• A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1

  2015cites this paper
• Immunosuppressive properties of mitomycin C-incubated human myeloid blood cells (MIC) in vitro.

  2015cites this paper
• Animal Models in Biomedical Research

  2015cites this paper
• What's new in clinical solid organ transplantation by 2013.

  2014cites this paper
• Macrophage Depletion by Free Bisphosphonates and Zoledronate-Loaded Red Blood Cells

  2014cites this paper