Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (741 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Tolerance, Transplantation; Allograft Tolerance; Tolerance, Allograft; Graft Tolerance; Tolerance, Graft.
Where it fits in the MeSH classification
- Broader topics
- Immune Tolerance
- See also
- Graft Survival
Research landscape
PubMed indexes 2,821 records tagged with the MeSH heading “Transplantation Tolerance” (counts retrieved 2026-10-29). 367 of them (13.0%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 1,286 records.
Reviews account for 1,004 records (35.6%) and meta-analyses for 1. Randomized controlled trials number 17 (0.6%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 7 |
| 2000-2009 | 1,286 |
| 2010-2019 | 1,161 |
| 2020 onward | 367 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,004 | 35.6% |
| Meta-analyses | 1 | 0.0% |
| Randomized controlled trials | 17 | 0.6% |
Method: PubMed query "Transplantation Tolerance"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in immunology
Immune responses are studied in model organisms, in cells from donors and in patients, and the same pathway can behave differently across these settings. Mouse immune systems differ from human ones in important ways, and blood measurements may not reflect what happens in tissues. Clinical conclusions about immune-mediated disease or immunotherapy come mainly from controlled trials and long-term cohorts. Check the species and tissue studied, whether markers were linked to outcomes patients notice, and the follow-up time.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Mesenchymal Stromal Cells for Transplant Tolerance | 2019 | Review article Design not recorded in structured metadata | 61 | cc by PMID 31231393 · DOI · PMC6559333 |
| Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction | 2020 | Review article Design not recorded in structured metadata | 50 | cc by PMID 32751357 · DOI · PMC7432796 |
| Transplant Tolerance Induction: Insights From the Liver | 2020 | Review article Design not recorded in structured metadata | 40 | cc by PMID 32582167 · DOI · PMC7289953 |
| T cell senescence induced by DNMT1 deletion mediates cardiac transplant tolerance via altered CDKN1A methylation | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 41691367 · DOI · PMC13239813 |
Mesenchymal Stromal Cells for Transplant Tolerance [1]
Abstract reading summary — source excerpts
- Opening excerpt
- In solid organ transplantation lifelong immunosuppression exposes transplant recipients to life-threatening complications, such as infections and malignancies, and to severe side effects.
- Closing excerpt
- We will also provide an overview of available data on safety and feasibility of MSC therapy in solid organ transplant patients, highlighting the issues that still need to be addressed before establishing MSC as a safe and effective tolerogenic cell therapy in transplantation.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (124 words)
In solid organ transplantation lifelong immunosuppression exposes transplant recipients to life-threatening complications, such as infections and malignancies, and to severe side effects. Cellular therapy with mesenchymal stromal cells (MSC) has recently emerged as a promising strategy to regulate anti-donor immune responses, allowing immunosuppressive drug minimization and tolerance induction. In this review we summarize preclinical data on MSC in solid organ transplant models, focusing on potential mechanisms of action of MSC, including down-regulation of effector T-cell response and activation of regulatory pathways. We will also provide an overview of available data on safety and feasibility of MSC therapy in solid organ transplant patients, highlighting the issues that still need to be addressed before establishing MSC as a safe and effective tolerogenic cell therapy in transplantation.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31231393 · DOI · PMC6559333
Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction [2]
Abstract reading summary — source excerpts
- Opening excerpt
- New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival.
- Closing excerpt
- Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (264 words)
New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a "molecular" diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of "immunoquiescent" or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32751357 · DOI · PMC7432796
Transplant Tolerance Induction: Insights From the Liver [3]
Abstract reading summary — source excerpts
- Opening excerpt
- A comparison of pre-clinical transplant models and of solid organs transplanted in routine clinical practice demonstrates that the liver is most amenable to the development of immunological tolerance.
- Closing excerpt
- In addition, we will address innovative therapeutic strategies, including mesenchymal stem cell, regulatory T cell, and regulatory dendritic cell therapy to promote liver allograft tolerance or minimization of immunosuppression in the clinic.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (179 words)
A comparison of pre-clinical transplant models and of solid organs transplanted in routine clinical practice demonstrates that the liver is most amenable to the development of immunological tolerance. This phenomenon arises in the absence of stringent conditioning regimens that accompany published tolerizing protocols for other organs, particularly the kidney. The unique immunologic properties of the liver have assisted our understanding of the alloimmune response and how it can be manipulated to improve graft function and survival. This review will address important findings following liver transplantation in both animals and humans, and how these have driven the understanding and development of therapeutic immunosuppressive options. We will discuss the liver's unique system of immune and non-immune cells that regulate immunity, yet maintain effective responses to pathogens, as well as mechanisms of liver transplant tolerance in pre-clinical models and humans, including current immunosuppressive drug withdrawal trials and biomarkers of tolerance. In addition, we will address innovative therapeutic strategies, including mesenchymal stem cell, regulatory T cell, and regulatory dendritic cell therapy to promote liver allograft tolerance or minimization of immunosuppression in the clinic.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32582167 · DOI · PMC7289953
T cell senescence induced by DNMT1 deletion mediates cardiac transplant tolerance via altered CDKN1A methylation [4]
Abstract reading summary — source excerpts
- Opening excerpt
- This study investigates the role of DNA methyltransferase 1 (DNMT1) in T cell senescence and heart transplant rejection using mouse models and clinical data.
- Closing excerpt
- DNMT1 may thus serve as a potential therapeutic target for heart transplant rejection.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (174 words)
This study investigates the role of DNA methyltransferase 1 (DNMT1) in T cell senescence and heart transplant rejection using mouse models and clinical data. In the mouse heart transplantation model, DNMT1 was found to be highly expressed in graft-infiltrating T cells. Using Dnmt1flox/floxCd4cre/+ mice, researchers demonstrated that T cell-specific knockout of DNMT1 led to long-term graft survival by impairing effector differentiation and promoting senescence in CD4+ T cells rather than in CD8+ T cells. Whole-genome methylation sequencing and RNA sequencing revealed that DNMT1 knockout decreased methylation of the cyclin-dependent kinase inhibitor 1A (CDKN1A) promoter, upregulating CDKN1A expression. Depletion of CDKN1Ahigh cells reversed DNMT1-inhibitor-induced T cell senescence. Clinically, increased T cell senescence was observed in post-transplant patients and is known to increase with age. Additionally, data from the UNOS database showed lower rejection rates in older recipients (age >65). These findings suggest that DNMT1 ablation accelerates CD4+ T cell senescence by altering CDKN1A methylation, thereby reducing T cell function and mitigating rejection. DNMT1 may thus serve as a potential therapeutic target for heart transplant rejection.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41691367 · DOI · PMC13239813
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article HLA-G: At the Interface of Maternal-Fetal Tolerance [5]
- Research article Inducing immune tolerance with dendritic cell-targeting nanomedicines [6]
- Research article Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs [7]
- Research article Xenotransplantation: immunological hurdles and progress toward tolerance [8]
- Research article Immunogenicity of pluripotent stem cells and their derivatives [9]
- Research article The need for minimization strategies: current problems of immunosuppression [10]
References
- Podestà MA, Remuzzi G, Casiraghi F. Mesenchymal Stromal Cells for Transplant Tolerance. . 2019. PMID 31231393 · DOI · PMC6559333
- Quaglia M, Merlotti G, Guglielmetti G, Castellano G, Cantaluppi V. Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction. . 2020. PMID 32751357 · DOI · PMC7432796
- Dai H, Zheng Y, Thomson AW, Rogers NM. Transplant Tolerance Induction: Insights From the Liver. . 2020. PMID 32582167 · DOI · PMC7289953
- Chen Y, Yim WY, Li C, Wang Z, Hou J, Peng Y, et al.. T cell senescence induced by DNMT1 deletion mediates cardiac transplant tolerance via altered CDKN1A methylation. . 2026. PMID 41691367 · DOI · PMC13239813
- Ferreira LMR, Meissner TB, Tilburgs T, Strominger JL. HLA-G: At the Interface of Maternal-Fetal Tolerance. Trends Immunol. 2017. PMID 28279591 · DOI
- Cifuentes-Rius A, Desai A, Yuen D, Johnston APR, Voelcker NH. Inducing immune tolerance with dendritic cell-targeting nanomedicines. Nat Nanotechnol. 2021. PMID 33349685 · DOI
- Sánchez-Fueyo A, Strom TB. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology. 2011. PMID 21073873 · DOI · PMC3866688
- Griesemer A, Yamada K, Sykes M. Xenotransplantation: immunological hurdles and progress toward tolerance. Immunol Rev. 2014. PMID 24517437 · DOI · PMC4023346
- de Almeida PE, Ransohoff JD, Nahid A, Wu JC. Immunogenicity of pluripotent stem cells and their derivatives. Circ Res. 2013. PMID 23371903 · DOI · PMC3638957
- Bamoulid J, Staeck O, Halleck F, Khadzhynov D, Brakemeier S, Dürr M, et al.. The need for minimization strategies: current problems of immunosuppression. Transpl Int. 2015. PMID 25752992 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.