ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
65 citing papers in PubMed, 87 citations in OpenAlex.
- T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection.PLoS pathogens · 2014Trial
- The CD8 immgenT framework as a universal reference of mouse CD8αβ T cell differentiation states.bioRxiv : the preprint server for biology · 2026Article
- Predicting Durable Anti-tumor Immune Responses after Cancer Vaccines.Journal of cancer immunology · 2026Article
- Severe malaria enforces short-lived effector cell differentiation but does not prevent effective secondary responses by memory CD8 T cells.PLoS pathogens · 2025Article
- Keeping it local: how CD8 TRMs regulate viral and cancer immunity.Frontiers in immunology · 2025Review
- Co-expression of IL-15/IL-15Ra complex enhances NKG2D-CAR T cell-mediated anti-pancreatic cancer immunity by activating the JAK/STAT5 signaling pathway.Frontiers in immunology · 2025Article
- Magnitude of antigen-specific T-cell immunity the month after completing vaccination series predicts the development of long-term persistence of antitumor immune response.Journal for immunotherapy of cancer · 2024Article
- Immunological Considerations for the Development of an Effective Herpes Vaccine.Microorganisms · 2024Review
- A review of CD4Veterinary immunology and immunopathology · 2024Review
- Tim-3 Is Not Required for Establishment of CD8+ T Cell Memory to Lymphocytic Choriomeningitis Virus.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Regulation of effector and memory CD8 + T cell differentiation: a focus on orphan nuclear receptor NR4A family, transcription factor, and metabolism.Immunologic research · 2023Review
- Intestinal CD8Mucosal immunology · 2021Article
- Conversations that count: Cellular interactions that drive T cell fate.Immunological reviews · 2021Review
- Down-regulation of EOMES drives T-cell exhaustion via abolishing EOMES-mediated repression of inhibitory receptors of T cells in liver cancer.Journal of cellular and molecular medicine · 2021Article
- Characterizing Hepatitis C Virus-Specific CD4Hepatology (Baltimore, Md.) · 2020Observational
- Type 1 TNature immunology · 2020Article
- Receptor signaling, transcriptional, and metabolic regulation of T cell exhaustion.Oncoimmunology · 2020Review
- T-bet Transcription Factor Promotes Antibody-Secreting Cell Differentiation by Limiting the Inflammatory Effects of IFN-γ on B Cells.Immunity · 2019Article
- Contrasting Roles of the PD-1 Signaling Pathway in Dendritic Cell-Mediated Induction and Regulation of HIV-1-Specific Effector T Cell Functions.Journal of virology · 2019Article
- Unique Type I Interferon, Expansion/Survival Cytokines, and JAK/STAT Gene Signatures of Multifunctional Herpes Simplex Virus-Specific Effector Memory CD8Journal of virology · 2019Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Memory CD8 T cells acquire effector memory cell properties after reinfection and may reach terminally differentiated, senescent states ("Hayflick limit") after multiple infections. The signals controlling this process are not well understood, but we found that the degree of secondary effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and preexisting memory CD8 T cell number (i.e., primary memory CD8 T cell precursor frequency) present during secondary infection. Compared with naive cells, memory CD8 T cells were predisposed toward terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of Ag. TE cell formation after secondary (2°) or tertiary infections was dependent on increased T-bet expression because T-bet(+/-) cells were resistant to these phenotypic changes. Larger numbers of preexisting memory CD8 T cells limited the duration of 2° infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2° TE CD8 T cells that formed. Together, these data show that over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with Ag or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by preexisting memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies.
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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.