ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Recall responses by helpless memory CD8+ T cells are restricted by the up-regulation of PD-1.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. 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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Who cites it
53 citing papers in PubMed, 69 citations in OpenAlex.
- Immune responses in chicken mucosal lymphoid tissues following oral and eye drop vaccination and revaccination with live modified vaccine of infectious laryngotracheitis virus (ILTV).Archives of virology · 2026Article
- Prolonged but finite antigen presentation promotes reversible defects of "helpless" memory CD8Immunity · 2025Article
- CD4+ T cell help during early acute hepacivirus infection is critical for viral clearance and the generation of a liver-homing CD103+CD49a+ effector CD8+ T cell subset.PLoS pathogens · 2024Article
- Role of lamin A/C on dendritic cell function in antiviral immunity.Cellular and molecular life sciences : CMLS · 2024Article
- Influenza Virus-Derived CD8 T Cell Epitopes: Implications for the Development of Universal Influenza Vaccines.Immune network · 2024Review
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
- Role of regulation of PD-1 and PD-L1 expression in sepsis.Frontiers in immunology · 2023Review
- Emerging concepts in PD-1 checkpoint biology.Seminars in immunology · 2021Review
- Inhibitory signaling sustains a distinct early memory CD8Science immunology · 2021Article
- The PD-1 Pathway Regulates Development and Function of Memory CD8Cell reports · 2020Article
- CD4 T cells control development and maintenance of brain-resident CD8 T cells during polyomavirus infection.PLoS pathogens · 2018Article
- CD70 encoded by modified vaccinia virus Ankara enhances CD8 T-cell-dependent protective immunity in MHC class II-deficient mice.Immunology · 2018Article
- PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- The diverse functions of the PD1 inhibitory pathway.Nature reviews. Immunology · 2018Review
- Regulation of GVHD and GVL Activity via PD-L1 Interaction With PD-1 and CD80.Frontiers in immunology · 2018Review
- The IL-1R/TLR signaling pathway is essential for efficient CD8Cellular & molecular immunology · 2017Article
- PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?Frontiers in immunology · 2017Review
- Demethylation of the PD-1 Promoter Is Imprinted during the Effector Phase of CD8 T Cell Exhaustion.Journal of virology · 2016Article
- Role of interferon-γ and cytotoxic T lymphocytes in intraocular tumor rejection.Journal of leukocyte biology · 2016Article
- CD4(+) T-cell dependence of primary CD8(+) T-cell response against vaccinia virus depends upon route of infection and viral dose.Cellular & molecular immunology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
CD4 help is crucial for memory CD8(+) T cell development, yet the mechanisms of CD4 help and why (CD4) helpless memory CD8(+) T cells elicit poor recall responses are currently not well understood. In this study we investigated these questions using an in vivo acute virus infection model. We show herein that CD4 help during priming is required for memory CD8(+) T cell differentiation, and that stimulation of CD40 during priming rescues the helpless defects in the absence of CD4(+) T cells. The defective recall response by helpless memory cells did not correlate with the amount of cell death and was independent of TRAIL. However, helpless memory cells excessively up-regulated the inhibitory receptor PD-1 (programmed cell death-1), and PD-1 blockade enhanced the recall response of helpless memory cells. Furthermore, providing IL-2 signaling in vivo during the recall response reduced PD-1 expression and rescued the recall response of helpless memory cells. Our study identifies molecular pathways involved in CD4 help for memory CD8(+) T cell generation that are independent of TRAIL, and it provides therapeutic implications that helpless memory cell function can be restored at multiple stages through various immunological interventions.
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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.