ArticleThe Journal of experimental medicine2012
Autoreactive T cells bypass negative selection and respond to self-antigen stimulation during infection.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 140 citations in OpenAlex.
- Stepwise epigenetic signal integration drives adaptive programming of cytotoxic lymphocytes.Immunity · 2026Article
- Antigen reactivity defines tissue-resident memory and exhausted T cells in tumors.Nature immunology · 2026Article
- B Cells Can Trigger the T-Cell-Mediated Autoimmune Response Against Melanocytes in Psoriasis.Cells · 2025Article
- Immune tolerance to foreign antigens in the intestine: mechanisms mediated by CD4＋ T cells.BMB reports · 2025Review
- Rheumatic heart valve disease: navigating the challenges of an overlooked autoimmune disorder.Frontiers in cardiovascular medicine · 2025Review
- Immune Checkpoint Inhibitor-Associated Cutaneous Adverse Events: Mechanisms of Occurrence.International journal of molecular sciences · 2024Review
- Low-affinity CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
- Zfp36l1 establishes the high-affinity CD8 T-cell response by directly linking TCR affinity to cytokine sensing.European journal of immunology · 2024Article
- The role of FoxM1 in immune cells.Clinical and experimental medicine · 2023Review
- Lymph node sharing between pancreas, gut, and liver leads to immune crosstalk and regulation of pancreatic autoimmunity.Immunity · 2023Article
- Tissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15.Science immunology · 2023Article
- Reprogramming the tumor microenvironment leverages CD8Molecular therapy oncolytics · 2023Article
- Single-cell fate mapping reveals widespread clonal ignorance of low-affinity T cells exposed to systemic infection.European journal of immunology · 2023Article
- Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development.Nature immunology · 2023Article
- IFN-γ-dependent tumor-antigen cross-presentation by lymphatic endothelial cells promotes their killing by T cells and inhibits metastasis.Science advances · 2022Article
- Variegated Outcomes of T Cell Activation by Dendritic Cells in the Steady State.Journal of immunology (Baltimore, Md. : 1950) · 2022Review
- T-Cell Responses to Immunodominant Listeria Epitopes Limit Vaccine-Directed Responses to the Colorectal Cancer Antigen, Guanylyl Cyclase C.Frontiers in immunology · 2022Article
- Defining and targeting patterns of T cell dysfunction in inborn errors of immunity.Frontiers in immunology · 2022Review
- Lymphopenia and Mechanisms of T-Cell Regeneration.Cell and tissue biology · 2022Article
- Strength and Numbers: The Role of Affinity and Avidity in the 'Quality' of T Cell Tolerance.Cells · 2021Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Central and peripheral tolerance prevent autoimmunity by deleting the most aggressive CD8(+) T cells but they spare cells that react weakly to tissue-restricted antigen (TRA). To reveal the functional characteristics of these spared cells, we generated a transgenic mouse expressing the TCR of a TRA-specific T cell that had escaped negative selection. Interestingly, the isolated TCR matches the affinity/avidity threshold for negatively selecting T cells, and when developing transgenic cells are exposed to their TRA in the thymus, only a fraction of them are eliminated but significant numbers enter the periphery. In contrast to high avidity cells, low avidity T cells persist in the antigen-positive periphery with no signs of anergy, unresponsiveness, or prior activation. Upon activation during an infection they cause autoimmunity and form memory cells. Unexpectedly, peptide ligands that are weaker in stimulating the transgenic T cells than the thymic threshold ligand also induce profound activation in the periphery. Thus, the peripheral T cell activation threshold during an infection is below that of negative selection for TRA. These results demonstrate the existence of a level of self-reactivity to TRA to which the thymus confers no protection and illustrate that organ damage can occur without genetic predisposition to autoimmunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.