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
Removal, via cell death, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.
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: Clonal Deletions; Deletion, Clonal; Deletions, Clonal; Clonal Abortion; Abortion, Clonal; Abortions, Clonal; Clonal Abortions.
Where it fits in the MeSH classification
- Broader topics
- Immune Tolerance
- See also
- Apoptosis
Related concepts
Research landscape
PubMed indexes 907 records tagged with the MeSH heading “Clonal Deletion” (counts retrieved 2026-10-29). 25 of them (2.8%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 406 records.
Reviews account for 212 records (23.4%) and meta-analyses for 0. Randomized controlled trials number 0 (0.0%) 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 | 349 |
| 2000-2009 | 406 |
| 2010-2019 | 127 |
| 2020 onward | 25 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 212 | 23.4% |
| Meta-analyses | 0 | 0.0% |
| Randomized controlled trials | 0 | 0.0% |
Method: PubMed query "Clonal Deletion"[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 |
|---|---|---|---|---|
| How autoreactive thymocytes differentiate into regulatory versus effector CD4+ T cells after avoiding clonal deletion | 2023 | Research article Design not recorded in structured metadata | 45 | cc by PMID 36959291 · DOI · PMC10063450 |
| B7-CD28 co-stimulation modulates central tolerance via thymic clonal deletion and Treg generation through distinct mechanisms | 2020 | Research article Design not recorded in structured metadata | 36 | cc by PMID 33293517 · DOI · PMC7722925 |
| Treg Therapies Revisited: Tolerance Beyond Deletion | 2020 | Review article Design not recorded in structured metadata | 30 | cc by PMID 33633742 · DOI · PMC7902070 |
| Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice | 2025 | Research article Design not recorded in structured metadata | 8 | cc by PMID 39824797 · DOI · PMC11742425 |
How autoreactive thymocytes differentiate into regulatory versus effector CD4+ T cells after avoiding clonal deletion [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Thymocytes bearing autoreactive T cell receptors (TCRs) are agonist-signaled by TCR/co-stimulatory molecules to either undergo clonal deletion or to differentiate into specialized regulatory T (Treg) or effector T (Teff) CD4+ cells.
- Closing excerpt
- Thus, TCR signaling disruption versus persistence is a general mechanism of lineage fate determination in the thymus that directs development of agonist-signaled autoreactive thymocytes.
- 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 (162 words)
Thymocytes bearing autoreactive T cell receptors (TCRs) are agonist-signaled by TCR/co-stimulatory molecules to either undergo clonal deletion or to differentiate into specialized regulatory T (Treg) or effector T (Teff) CD4+ cells. How these different fates are achieved during development remains poorly understood. We now document that deletion and differentiation are agonist-signaled at different times during thymic selection and that Treg and Teff cells both arise after clonal deletion as alternative lineage fates of agonist-signaled CD4+CD25+ precursors. Disruption of agonist signaling induces CD4+CD25+ precursors to initiate Foxp3 expression and become Treg cells, whereas persistent agonist signaling induces CD4+CD25+ precursors to become IL-2+ Teff cells. Notably, we discovered that transforming growth factor-β induces Foxp3 expression and promotes Treg cell development by disrupting weaker agonist signals and that Foxp3 expression is not induced by IL-2 except under non-physiological in vivo conditions. Thus, TCR signaling disruption versus persistence is a general mechanism of lineage fate determination in the thymus that directs development of agonist-signaled autoreactive thymocytes.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36959291 · DOI · PMC10063450
B7-CD28 co-stimulation modulates central tolerance via thymic clonal deletion and Treg generation through distinct mechanisms [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The molecular and cellular mechanisms mediating thymic central tolerance and prevention of autoimmunity are not fully understood.
- Closing excerpt
- Our findings thus reveal a function of B7-CD28 co-stimulation in shaping the T cell repertoire and limiting autoimmunity through both thymic clonal deletion and Treg cell generation.
- 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 (137 words)
The molecular and cellular mechanisms mediating thymic central tolerance and prevention of autoimmunity are not fully understood. Here we show that B7-CD28 co-stimulation and B7 expression by specific antigen-presenting cell (APC) types are required for clonal deletion and for regulatory T (Treg) cell generation from endogenous tissue-restricted antigen (TRA)-specific thymocytes. While B7-CD28 interaction is required for both clonal deletion and Treg induction, these two processes differ in their CD28 signaling requirements and in their dependence on B7-expressing dendritic cells, B cells, and thymic epithelial cells. Meanwhile, defective thymic clonal deletion due to altered B7-CD28 signaling results in the accumulation of mature, peripheral TRA-specific T cells capable of mediating destructive autoimmunity. Our findings thus reveal a function of B7-CD28 co-stimulation in shaping the T cell repertoire and limiting autoimmunity through both thymic clonal deletion and Treg cell generation.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33293517 · DOI · PMC7722925
Treg Therapies Revisited: Tolerance Beyond Deletion [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Induction of immune tolerance is the Holy Grail in transplantation medicine and autoimmunity.
- Closing excerpt
- We also mention new questions arising from the first clinical studies on Treg therapy in the fields of transplantation and autoimmunity.
- 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 (237 words)
Induction of immune tolerance is the Holy Grail in transplantation medicine and autoimmunity. Currently, patients are required to use immunosuppressive drugs for the rest of their lives, resulting in unwanted side effects and complication from global suppression of the immune response. It is well established that regulatory T cells (Tregs) are critical for the maintenance of immune tolerance towards self-antigens by several mechanisms of immune regulation, in parallel with intrathymic deletion of self-reactive T cells during ontogeny. Therefore, approaches for increasing Treg numbers or function in vivo could provide an all-purpose solution for tolerance induction. Currently, most state-of-the-art therapeutics for treating autoimmune diseases or preventing allograft rejection work either by general immunosuppression or blocking inflammatory reactions and are non-specific. Hence, these approaches cannot provide satisfactory long-term results, let alone a cure. However, in animal models the therapeutic potential of Treg expansion for inducing effective tolerance has now been demonstrated in various models of autoimmunity and allogeneic transplantation. Here, we focus on therapies for increasing the size of the Treg pool by expanding endogenous Treg numbers in vivo or by adoptive transfer of Tregs. In particular, we discuss IL-2 based approaches (low dose IL-2, IL-2 complexes) for inducing Treg expansion in vivo as well as cell-based approaches (polyclonal, antigen specific, or cell engineered) for adoptive Treg therapy. We also mention new questions arising from the first clinical studies on Treg therapy in the fields of transplantation and autoimmunity.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33633742 · DOI · PMC7902070
Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice [4]
Abstract reading summary — source excerpts
- Opening excerpt
- The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear.
- Closing excerpt
- We further show that the Nr4a family helps mediate a broad transcriptional program in self-reactive thymocytes that resembles anergy and may operate at the margins of canonical thymic tolerance mechanisms to restrain self-reactive T cells after thymic egress.
- 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 (149 words)
The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen. Importantly, thymocytes lacking Nr4a1/3 acquire an anergy-like signature after escaping clonal deletion and Treg lineage diversion. We further show that the Nr4a family helps mediate a broad transcriptional program in self-reactive thymocytes that resembles anergy and may operate at the margins of canonical thymic tolerance mechanisms to restrain self-reactive T cells after thymic egress.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39824797 · DOI · PMC11742425
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 The somatic generation of immune recognition [5]
- Research article Activation-induced cell death in T cells [6]
- Research article Central tolerance: learning self-control in the thymus [7]
- Research article Negative selection--clearing out the bad apples from the T-cell repertoire [8]
- Research article The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function [9]
- Research article Thymic selection revisited: how essential is it? [10]
References
- Tai X, Indart A, Rojano M, Guo J, Apenes N, Kadakia T, et al.. How autoreactive thymocytes differentiate into regulatory versus effector CD4+ T cells after avoiding clonal deletion. . 2023. PMID 36959291 · DOI · PMC10063450
- Watanabe M, Lu Y, Breen M, Hodes RJ. B7-CD28 co-stimulation modulates central tolerance via thymic clonal deletion and Treg generation through distinct mechanisms. . 2020. PMID 33293517 · DOI · PMC7722925
- Pilat N, Sprent J. Treg Therapies Revisited: Tolerance Beyond Deletion. . 2020. PMID 33633742 · DOI · PMC7902070
- Nielsen HV, Yang L, Mueller JL, Ritter AJ, Hiwa R, Proekt I, et al.. Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice. . 2025. PMID 39824797 · DOI · PMC11742425
- Jerne NK. The somatic generation of immune recognition. Eur J Immunol. 1971. PMID 14978855 · DOI
- Green DR, Droin N, Pinkoski M. Activation-induced cell death in T cells. Immunol Rev. 2003. PMID 12752672 · DOI
- Hogquist KA, Baldwin TA, Jameson SC. Central tolerance: learning self-control in the thymus. Nat Rev Immunol. 2005. PMID 16200080 · DOI
- Palmer E. Negative selection--clearing out the bad apples from the T-cell repertoire. Nat Rev Immunol. 2003. PMID 12766760 · DOI
- Hogquist KA, Jameson SC. The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function. Nat Immunol. 2014. PMID 25137456 · DOI · PMC4348363
- von Boehmer H, Aifantis I, Gounari F, Azogui O, Haughn L, Apostolou I, et al.. Thymic selection revisited: how essential is it?. Immunol Rev. 2003. PMID 12614352 · 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.