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 (685 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
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
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, Immune; Immunosuppression (Physiology); Immunosuppressions (Physiology).
Where it fits in the MeSH classification
- Broader topics
- Immunomodulation
- Narrower topics
- Clonal Anergy; Clonal Deletion; Endotoxin Tolerance; Immune Privilege; Self Tolerance; Tachyphylaxis; Transplantation Tolerance
- See also
- Graft vs Host Disease; Immunosuppression Therapy; Immunocompromised Host
Research landscape
PubMed indexes 48,717 records tagged with the MeSH heading “Immune Tolerance” (counts retrieved 2026-10-29). 4,931 of them (10.1%) were published from 2020 onward, and the busiest period so far is through 1999 with 20,787 records.
Reviews account for 12,757 records (26.2%) and meta-analyses for 33. Randomized controlled trials number 364 (0.7%) 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 | 20,787 |
| 2000-2009 | 11,276 |
| 2010-2019 | 11,723 |
| 2020 onward | 4,931 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 12,757 | 26.2% |
| Meta-analyses | 33 | 0.1% |
| Randomized controlled trials | 364 | 0.7% |
Method: PubMed query "Immune 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 |
|---|---|---|---|---|
| Sepsis-induced immunosuppression: mechanisms, biomarkers and immunotherapy | 2025 | Review article Design not recorded in structured metadata | 89 | cc by PMID 40364841 · DOI · PMC12069044 |
| Identification of antigen-presenting cell-T cell interactions driving immune responses to food | 2025 | Research article Design not recorded in structured metadata | 68 | cc by PMID 39700315 · DOI · PMC12017586 |
| PRDM16-dependent antigen-presenting cells induce tolerance to gut antigens | 2025 | Research article Design not recorded in structured metadata | 58 | cc by PMID 40228524 · DOI · PMC12176658 |
| Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance | 2026 | Research article Design not recorded in structured metadata | 18 | cc by PMID 41616773 · DOI · PMC13289805 |
Sepsis-induced immunosuppression: mechanisms, biomarkers and immunotherapy [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Sepsis, a life-threatening organ dysfunction resulting from a dysregulated host response to infection, initiates a complex immune response that varies over time, characterized by sustained excessive inflammation and immunosuppression.
- Closing excerpt
- Here, our review highlights the mechanisms of sepsis-induced immunosuppression and current diagnostic biomarkers, as well as immune-enhancing strategies evaluated in septic patients and therapeutics under investigation.
- 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 (132 words)
Sepsis, a life-threatening organ dysfunction resulting from a dysregulated host response to infection, initiates a complex immune response that varies over time, characterized by sustained excessive inflammation and immunosuppression. Sepsis-induced immunosuppression is now recognized as a major cause of septic death, and identifying effective strategies to counteract it poses a significant challenge. This immunosuppression results from the disruption of immune homeostasis, characterized by the abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, release of anti-inflammatory cytokines, and expression of immune checkpoints. Preclinical studies targeting immunosuppression, particularly with immune checkpoint inhibitors, have shown promise in reversing immunocyte dysfunctions and establishing host resistance to pathogens. Here, our review highlights the mechanisms of sepsis-induced immunosuppression and current diagnostic biomarkers, as well as immune-enhancing strategies evaluated in septic patients and therapeutics under investigation.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40364841 · DOI · PMC12069044
Identification of antigen-presenting cell-T cell interactions driving immune responses to food [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens.
- Closing excerpt
- These inflammatory cDC2s expanded by helminth infection did not present dietary antigens, thus avoiding diet-specific Th2 responses.
- 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 (128 words)
The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal antigens to CD4+ T cells and inducing their differentiation into regulatory (peripheral regulatory T cell) or inflammatory [T helper (Th) cell] subsets. We used a proximity labeling method (LIPSTIC) to identify APCs that presented dietary antigens under tolerizing and inflammatory conditions and to understand cellular mechanisms by which tolerance to food is induced and can be disrupted by infection. Helminth infections disrupted tolerance induction proportionally to the reduction in the ratio between tolerogenic APCs-including migratory dendritic cells (cDC1s) and Rorγt+ APCs-and inflammatory APCs, which were primarily cDC2s. These inflammatory cDC2s expanded by helminth infection did not present dietary antigens, thus avoiding diet-specific Th2 responses.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39700315 · DOI · PMC12017586
PRDM16-dependent antigen-presenting cells induce tolerance to gut antigens [3]
Abstract reading summary — source excerpts
- Opening excerpt
- The gastrointestinal tract is continuously exposed to foreign antigens in food and commensal microorganisms with potential to induce adaptive immune responses.
- Closing excerpt
- Our findings suggest that a better understanding of how tolDCs develop and how they regulate T cell responses to food and microbial antigens could offer new insights into developing therapeutic strategies for autoimmune and allergic diseases as well as organ transplant tolerance.
- 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 (274 words)
The gastrointestinal tract is continuously exposed to foreign antigens in food and commensal microorganisms with potential to induce adaptive immune responses. Peripherally induced T regulatory (pTreg) cells are essential for mitigating inflammatory responses to these agents1-4. Although RORγt+ antigen-presenting cells (APCs) have been shown to programme gut microbiota-specific pTreg cells5-7, their definition remains incomplete, and the APC responsible for food tolerance has remained unknown. Here we identify an APC subset that is required for differentiation of both food- and microbiota-specific pTreg cells and for establishment of oral tolerance. Development and function of these APCs require expression of the transcription factors PRDM16 and RORγt, as well as a unique Rorc(t) cis-regulatory element. Gene expression, chromatin accessibility, and surface marker analysis establish the pTreg-inducing APCs as myeloid in origin, distinct from type 3 innate lymphoid cells, and sharing epigenetic profiles with classical dendritic cells, and designate them PRDM16+RORγt+ tolerizing dendritic cells (tolDCs). Upon genetic perturbation of tolDCs, we observe a substantial increase in food antigen-specific T helper 2 cells in lieu of pTreg cells, leading to compromised tolerance in mouse models of asthma and food allergy. Single-cell analyses of freshly resected mesenteric lymph nodes from a human organ donor, as well as multiple specimens of human intestine and tonsil, reveal candidate tolDCs with co-expression of PRDM16 and RORC and an extensive transcriptome shared with tolDCs from mice, highlighting an evolutionarily conserved role across species. Our findings suggest that a better understanding of how tolDCs develop and how they regulate T cell responses to food and microbial antigens could offer new insights into developing therapeutic strategies for autoimmune and allergic diseases as well as organ transplant tolerance.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40228524 · DOI · PMC12176658
Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Lymph node (LN) colonization in cancer is linked to poor prognosis.
- Closing excerpt
- Hence, our findings establish LN colonization as an active driver of systemic immunosuppression, facilitating metastatic progression.
- 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 (151 words)
Lymph node (LN) colonization in cancer is linked to poor prognosis. Evidence suggests that LN colonization induces systemic immunosuppression, facilitating distant metastasis. We investigated LN-mediated immunosuppression in patients with head-and-neck cancer using spatial proteomics, spatial transcriptomics, and an in vivo model of melanoma LN metastasis. Both primary tumors and paired LNs of nodal-positive patients exhibit enhanced interferon-γ signaling and an enrichment of immunosuppressive myeloid cells and cancer-associated fibroblasts (CAFs). The spatial intersection of these myeloid-CAF-enriched niches with perifollicular T cell zones and LN follicles is linked to enhanced T cell dysfunction and Treg activation therein, thereby driving architectural LN remodeling. These immune suppressive changes extend to adjacent non-tumor-involved LN regions and nearby tumor-free LNs, but were not detected in LNs of non-cancer patients, reflecting a systemic effect that compromises anti-tumor immunity beyond the tumor-involved LN. Hence, our findings establish LN colonization as an active driver of systemic immunosuppression, facilitating metastatic progression.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41616773 · DOI · PMC13289805
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 Therapeutic cancer vaccines [5]
- Research article Dendritic Cell Regulation of T Helper Cells [6]
- Research article Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes [7]
- Research article Inducing immune tolerance with dendritic cell-targeting nanomedicines [8]
- Research article Macrophage Biology and Mechanisms of Immune Suppression in Breast Cancer [9]
- Research article Function and Role of Regulatory T Cells in Rheumatoid Arthritis [10]
References
- Gao X, Cai S, Li X, Wu G. Sepsis-induced immunosuppression: mechanisms, biomarkers and immunotherapy. . 2025. PMID 40364841 · DOI · PMC12069044
- Campos Canesso MC, de Castro TBR, Nakandakari-Higa S, Lockhart A, Luehr J, Bortolatto J, et al.. Identification of antigen-presenting cell-T cell interactions driving immune responses to food. . 2025. PMID 39700315 · DOI · PMC12017586
- Fu L, Upadhyay R, Pokrovskii M, Chen FM, Romero-Meza G, Griesemer A, et al.. PRDM16-dependent antigen-presenting cells induce tolerance to gut antigens. . 2025. PMID 40228524 · DOI · PMC12176658
- Haist M, Baertsch MA, Reticker-Flynn NE, Lu G, Kempchen TN, Chu P, et al.. Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance. . 2026. PMID 41616773 · DOI · PMC13289805
- Saxena M, van der Burg SH, Melief CJM, Bhardwaj N. Therapeutic cancer vaccines. Nat Rev Cancer. 2021. PMID 33907315 · DOI
- Yin X, Chen S, Eisenbarth SC. Dendritic Cell Regulation of T Helper Cells. Annu Rev Immunol. 2021. PMID 33710920 · DOI
- Huinen ZR, Huijbers EJM, van Beijnum JR, Nowak-Sliwinska P, Griffioen AW. Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes. Nat Rev Clin Oncol. 2021. PMID 33833434 · 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
- Mehta AK, Kadel S, Townsend MG, Oliwa M, Guerriero JL. Macrophage Biology and Mechanisms of Immune Suppression in Breast Cancer. Front Immunol. 2021. PMID 33968034 · DOI · PMC8102870
- Jiang Q, Yang G, Liu Q, Wang S, Cui D. Function and Role of Regulatory T Cells in Rheumatoid Arthritis. Front Immunol. 2021. PMID 33868244 · DOI · PMC8047316
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.