ArticleProceedings of the National Academy of Sciences of the United States of America2012
Notch controls the magnitude of T helper cell responses by promoting cellular longevity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The trial behind it
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
37 citing papers in PubMed.
- Notch2-expressing CD4Cellular & molecular immunology · 2025Article
- SARS-CoV-2 inflammation durably imprints memory CD4 T cells.Science immunology · 2024Article
- Tissue-resident memory T cells: decoding intra-organ diversity with a gut perspective.Inflammation and regeneration · 2024Review
- Inflammation durably imprints memory CD4+ T cells.bioRxiv : the preprint server for biology · 2023Article
- Late-onset neonatal sepsis: genetic differences by sex and involvement of the NOTCH pathway.Pediatric research · 2023Article
- Genetic architecture of innate and adaptive immune cells in pigs.Frontiers in immunology · 2023Article
- Mucosal Vaccination with Cyclic Dinucleotide Adjuvants Induces Effective T Cell Homing and IL-17-Dependent Protection againstJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Insights into T-cell dysfunction in Alzheimer's disease.Aging cell · 2021Review
- Notch signalling in T cell homeostasis and differentiation.Open biology · 2019Review
- JAG2/Notch2 inhibits intervertebral disc degeneration by modulating cell proliferation, apoptosis, and extracellular matrix.Arthritis research & therapy · 2019Article
- Notch Signaling Orchestrates Helminth-Induced Type 2 Inflammation.Trends in immunology · 2019Review
- NOTCH1 Represses MCL-1 Levels in GSI-resistant T-ALL, Making them Susceptible to ABT-263.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- The emerging role of ADAM metalloproteinases in immunity.Nature reviews. Immunology · 2018Review
- Notch signaling triggered via the ligand DLL4 impedes M2 macrophage differentiation and promotes their apoptosis.Cell communication and signaling : CCS · 2018Article
- CD4+ Memory T Cells at Home in the Tissue: Mechanisms for Health and Disease.Frontiers in immunology · 2018Review
- T Cell-Restricted Notch Signaling Contributes to Pulmonary Th1 and Th2 Immunity duringJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- Notch Signaling in T Helper Cell Subsets: Instructor or Unbiased Amplifier?Frontiers in immunology · 2017Review
- Programs for the persistence, vigilance and control of human CD8Nature immunology · 2016Article
- Targeting the Notch Pathway to Prevent Rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016Review
- Transmission of survival signals through Delta-like 1 on activated CD4Scientific reports · 2016Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Generation of effective immune responses requires expansion of rare antigen-specific CD4(+) T cells. The magnitude of the responding population is ultimately determined by proliferation and survival. Both processes are tightly controlled to limit responses to innocuous antigens. Sustained expansion occurs only when innate immune sensors are activated by microbial stimuli or by adjuvants, which has important implications for vaccination. The molecular identity of the signals controlling sustained T-cell responses is not fully clear. Here, we describe a prominent role for the Notch pathway in this process. Coactivation of Notch allows accumulation of far greater numbers of activated CD4(+) T cells than stimulation via T-cell receptor and classic costimulation alone. Notch does not overtly affect cell cycle entry or progression of CD4(+) T cells. Instead, Notch protects activated CD4(+) T cells against apoptosis after an initial phase of clonal expansion. Notch induces a broad antiapoptotic gene expression program that protects against intrinsic, as well as extrinsic, apoptosis pathways. Both Notch1 and Notch2 receptors and the canonical effector RBPJ (recombination signal binding protein for immunoglobulin kappa J region) are involved in this process. Correspondingly, CD4(+) T-cell responses to immunization with protein antigen are strongly reduced in mice lacking these components of the Notch pathway. Our findings, therefore, show that Notch controls the magnitude of CD4(+) T-cell responses by promoting cellular longevity.
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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.