ArticleProceedings of the National Academy of Sciences of the United States of America2019
Proliferation-competent Tcf1+ CD8 T cells in dysfunctional populations are CD4 T cell help independent.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Interpretation of T cell states from single-cell transcriptomics data using reference atlases.Nature communications · 2021Pooled it
- Stem-like PD-1Journal for immunotherapy of cancer · 2026Article
- Expansion and mobilization of virus-specific stem-like CD8 T cells in chronic viral infection after treatment with a long-acting IL-7, NT-I7.Cell reports · 2026Article
- Stepwise differentiation from precursor intermediates and distinct Th1 checkpoints promote CD4 Th1 cell differentiation during chronic viral infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lymph nodes fuel KLF2-dependent effector CD8Nature immunology · 2025Article
- The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1Immunity · 2025Article
- A specific microbial consortium enhances Th1 immunity, improves LCMV viral clearance but aggravates LCMV disease pathology in mice.Nature communications · 2025Article
- Architects of immunity: How dendritic cells shape CD8Science immunology · 2025Review
- The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation.Science immunology · 2024Article
- Cell Identity and Spatial Distribution of PD-1/PD-L1 Blockade Responders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- T cell dysfunction and therapeutic intervention in cancer.Nature immunology · 2024Review
- CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8Immunity · 2024Article
- Stem-like exhausted and memory CD8Nature reviews. Cancer · 2023Review
- Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming.Nature communications · 2023Article
- The Role of CD4 T Cell Help in CD8 T Cell Differentiation and Function During Chronic Infection and Cancer.Immune network · 2023Review
- Loss of PBAF promotes expansion and effector differentiation of CD8Cell reports · 2023Article
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
- Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8Nature immunology · 2023Article
- Exhausted CD8Trends in immunology · 2023Review
- Clonal lineage tracing reveals mechanisms skewing CD8+ T cell fate decisions in chronic infection.The Journal of experimental medicine · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
T cell maintenance in chronic infection and cancer follows a hierarchical order. Short-lived effector CD8 T cells are constitutively replaced from a proliferation-competent Tcf1-expressing progenitor population. This occurs spontaneously at low levels and increases in magnitude upon blocking PD-1 signaling. We explore how CD4 T cell help controls transition and survival of the progenitors and their progeny by utilizing single-cell RNA sequencing. Unexpectedly, absence of CD4 help caused reductions in cell numbers only among terminally differentiated cells while proliferation-competent progenitor cells remained unaffected with regard to their numbers and their overall phenotype. In fact, upon restoration of a functional CD4 compartment, the progenitors began to regenerate the effector CD8 T cells. Thus, unlike memory T cells for which secondary expansion requires CD4 T cell help, this is not a necessity for proliferation-competent progenitor cells in dysfunctional populations. Our data therefore reveals that proliferation-competent cells in dysfunctional populations show a previously unrecognized uncoupling of CD4 T cell help that is otherwise required by conventional memory T cells.
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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 Socratic graph.