ArticleProceedings of the National Academy of Sciences of the United States of America2012
Distinct CD4+ helper T cells involved in primary and secondary responses to infection.
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 53 papers.
What it found
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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
53 citing papers in PubMed, 75 citations in OpenAlex.
- Calibrating T cell responsiveness through interactions with self.Nature reviews. Immunology · 2026Review
- A Dapl1Science advances · 2025Article
- Cathepsin L-dependent positive selection shapes clonal composition and functional fitness of CD4Nature immunology · 2025Article
- Article
- Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development.The Journal of experimental medicine · 2024Review
- Precursor central memory versus effector cell fate and naïve CD4+ T cell heterogeneity.The Journal of experimental medicine · 2024Article
- CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses.Science (New York, N.Y.) · 2023Article
- The perception and response of T cells to a changing environment are based on the law of initial value.Science signaling · 2022Review
- Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections.Frontiers in immunology · 2022Article
- Functional heterogeneity and adaptation of naive T cells in response to tonic TCR signals.Current opinion in immunology · 2021Review
- Strength and Numbers: The Role of Affinity and Avidity in the 'Quality' of T Cell Tolerance.Cells · 2021Review
- CD5 levels define functionally heterogeneous populations of naïve human CD4European journal of immunology · 2021Article
- T cell self-reactivity during thymic development dictates the timing of positive selection.eLife · 2021Article
- Conversion of effector CD4Cellular & molecular immunology · 2021Article
- Adapting T Cell Receptor Ligand Discrimination CapabilityFrontiers in immunology · 2021Review
- Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions.Nature immunology · 2020Article
- Tonic TCR Signaling Inversely Regulates the Basal Metabolism of CD4ImmunoHorizons · 2020Article
- Manipulating the TCR signaling network for cellular immunotherapy: Challenges & opportunities.Molecular immunology · 2020Review
- Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells.Cell reports · 2020Article
- CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Helper T cells are critical for protective immunity, CD8(+) T-cell memory, and CD4(+) recall responses, but whether the same or distinct CD4(+) T cells are involved in these responses has not been established. Here we describe two CD4(+) T cells, LLO118 and LLO56, specific for an immunodominant Listeria monocytogenes epitope, with dramatically different responses to primary and secondary infection. Comparing in vivo responses, LLO118 T cells proliferate more strongly to primary infection, whereas surprisingly, LLO56 has a superior CD4(+) recall response to secondary infection. LLO118 T cells provide more robust help for CD8(+) T-cell responses to secondary infection than LLO56. We found no detectable differences in antigen sensitivity, but naive LLO118 T cells have much lower levels of CD5 and their T-cell receptor levels are dramatically down-regulated after their strong primary response. Thus, distinct CD4(+) helper T cells are specialized to help either in primary or secondary responses to infection.
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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.