ArticleThe Journal of experimental medicine2003
The strength of persistent antigenic stimulation modulates adaptive tolerance in peripheral CD4+ T cells.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 93 citations in OpenAlex.
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- Epitope-based precision immunotherapy of Type 1 diabetes.Human vaccines & immunotherapeutics · 2023Article
- Quantitative contributions of TNF receptor superfamily members to CD8Molecular systems biology · 2021Article
- Perfect adaptation of CD8Science signaling · 2021Article
- CD4AIDS research and human retroviruses · 2018Review
- Both inflammatory and regulatory cytokine responses to malaria are blunted with increasing age in highly exposed children.Malaria journal · 2017Article
- Density dependent re-tuning of autoreactive T cells alleviates their pathogenicity in a lymphopenic environment.Immunology letters · 2017Article
- Patterns of inflammatory responses and parasite tolerance vary with malaria transmission intensity.Malaria journal · 2017Article
- Long-term exposure to Myozyme results in a decrease of anti-drug antibodies in late-onset Pompe disease patients.Scientific reports · 2016Article
- Self-reactivity as the necessary cost of maintaining a diverse memory T-cell repertoire.Pathogens and disease · 2016Review
- Mechanisms of autoimmunity in the non-obese diabetic mouse: effector/regulatory cell equilibrium during peak inflammation.Immunology · 2016Review
- Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice.Nature communications · 2016Article
- Rapid proliferation of activated lymph node CD4(+) T cells is achieved by greatly curtailing the duration of gap phases in cell cycle progression.Cellular & molecular biology letters · 2014Article
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- Functionally responsive self-reactive B cells of low affinity express reduced levels of surface IgM.European journal of immunology · 2014Article
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- Insufficient autoantigen presentation and failure of tolerance in a mouse model of rheumatoid arthritis.Arthritis and rheumatism · 2013Article
- Article
- Subsets of nonclonal neighboring CD4+ T cells specifically regulate the frequency of individual antigen-reactive T cells.Immunity · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The quantitative adaptation of receptor thresholds allows cells to tailor their responses to changes in ambient ligand concentration in many biological systems. Such a cell-intrinsic calibration of T cell receptor (TCR) sensitivity could be involved in regulating responses to autoantigens, but this has never been demonstrated for peripheral T cells. We examined the ability of monoclonal naive T cells to modulate their responsiveness differentially after exposure to fourfold different levels of persistent antigen stimulation in vivo. T cells expanded and entered a tolerant state with different kinetics in response to the two levels of stimulation, but eventually adjusted to a similar slow rate of turnover. In vivo restimulation revealed a greater impairment in the proliferative ability of T cells resident in a higher antigen presentation environment. We also observed subtle differences in TCR signaling and in vitro cytokine production consistent with differential adaptation. Unexpectedly, the system failed to similarly compensate to the persistent stimulus in vivo at the level of CD69 expression and actin polymerization. This greater responsiveness of T cells residing in a host with a lower level of antigen presentation allows us to demonstrate for the first time an intrinsic tuning process in mature T lymphocytes, albeit one more complex than current theories predict.
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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.