ArticleThe Journal of experimental medicine2016
Blimp-1-mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 89 citations in OpenAlex.
- Upregulation of cellular exhaustion-related genes and CD4 + T cell disturbances in immunological non-responders on antiretroviral therapy.Immunologic research · 2026Article
- Spatial Transcriptomic Profiling Reveals Microenvironment-Dependent Immune Signatures in a Lyme Arthritis model.bioRxiv : the preprint server for biology · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting Mettl8-Tcf1 axis promotes CD8+ TPEX differentiation and antitumor immunity.The Journal of experimental medicine · 2026Article
- Blockade of Tim-3 pathway in a mouse model of Toxoplasmosis: impact on brain leukocyte infiltration, parasite burden, and neuroinflammation.Scientific reports · 2026Article
- T cell exhaustion in parasitic infections.Frontiers in immunology · 2026Review
- Cell-intrinsic CD4 T cell tolerance: a new frontier in therapy?Trends in immunology · 2025Review
- Miniaturized scalable arrayed CRISPR screening in primary cells enables discovery at the single donor resolution.Scientific reports · 2025Article
- Review
- In a model of parasite-mediated exhaustion, stem-like CD8 T cells differentiate into an unconventional intermediate effector memory subset.bioRxiv : the preprint server for biology · 2025Article
- Supercharging CAR-T cells through transcriptional and epigenetic armoring.Theranostics · 2025Review
- Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death.International immunology · 2024Review
- Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latentProceedings of the National Academy of Sciences of the United States of America · 2024Article
- PD-1 defines a distinct, functional, tissue-adapted state in Vδ1Nature cancer · 2024Article
- A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells.The EMBO journal · 2023Article
- A T follicular helper cell origin for T regulatory type 1 cells.Cellular & molecular immunology · 2023Article
- Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Recent Advances in the Development of Adenovirus-Vectored Vaccines for Parasitic Infections.Pharmaceuticals (Basel, Switzerland) · 2023Review
- A Lower Dose of Infection Generates a Better Long-Term Immune Response against Toxoplasma gondii.ImmunoHorizons · 2023Article
- Regulation of CD4 T Cell Responses by the Transcription Factor Eomesodermin.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)-susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell-intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches.
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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.