ArticleThe Journal of clinical investigation2016
TGF-β receptor maintains CD4 T helper cell identity during chronic viral infections.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Compensatory relationships determine the impact of TGF-β on the humoral immune response to hepatitis B surface antigen.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- HIV-1 Vpr orchestrates ciTRAN upregulation through TGF-β induction.PLoS pathogens · 2025Article
- Therapeutic targeting of TGF-β in lung cancer.The FEBS journal · 2025Review
- Prothrombin prevents fatal T cell-dependent anemia during chronic virus infection of mice.JCI insight · 2025Article
- Double, double toil and trouble: transforming growth factor beta (TGF-β) in HIV infection.Frontiers in immunology · 2025Review
- TGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo.Nature communications · 2024Article
- Transforming Growth Factor β Signaling Promotes HIV-1 Infection in Activated and Resting Memory CD4Journal of virology · 2023Article
- IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection.Frontiers in immunology · 2023Article
- The diverse effects of transforming growth factor-β and SMAD signaling pathways during the CTL response.Frontiers in immunology · 2023Review
- TGF-β regulates the stem-like state of PD-1+ TCF-1+ virus-specific CD8 T cells during chronic infection.The Journal of experimental medicine · 2022Article
- A CD4eLife · 2022Article
- Chicken Peripheral Blood Mononuclear Cells Response to Avian Leukosis Virus Subgroup J Infection Assessed by Single-Cell RNA Sequencing.Frontiers in microbiology · 2022Article
- The Role of ZEB2 in Human CD8 T Lymphocytes: Clinical and Cellular Immune Profiling in Mowat-Wilson Syndrome.International journal of molecular sciences · 2021Article
- TGFβ restricts expansion, survival, and function of T cells within the tuberculous granuloma.Cell host & microbe · 2021Article
- TGF-β and Eomes control the homeostasis of CD8+ regulatory T cells.The Journal of experimental medicine · 2021Article
- Consequences of Mutations and Abnormal Expression of SMAD4 in Tumors and T Cells.OncoTargets and therapy · 2021Review
- SKI and SMAD4 are essential for IL-21-induced Th17 differentiation.Molecular immunology · 2019Article
- Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus.Viruses · 2019Review
- IL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors.ImmunoHorizons · 2019Article
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Suppression of CD8 and CD4 T cells is a hallmark in chronic viral infections, including hepatitis C and HIV. While multiple pathways are known to inhibit CD8 T cells, the host molecules that restrict CD4 T cell responses are less understood. Here, we used inducible and CD4 T cell-specific deletion of the gene encoding the TGF-β receptor during chronic lymphocytic choriomeningitis virus infection in mice, and determined that TGF-β signaling restricted proliferation and terminal differentiation of antiviral CD4 T cells. TGF-β signaling also inhibited a cytotoxic program that includes granzymes and perforin expression at both early and late stages of infection in vivo and repressed the transcription factor eomesodermin. Overexpression of eomesodermin was sufficient to recapitulate in great part the phenotype of TGF-β receptor-deficient CD4 T cells, while SMAD4 was necessary for CD4 T cell accumulation and differentiation. TGF-β signaling also restricted accumulation and differentiation of CD4 T cells and reduced the expression of cytotoxic molecules in mice and humans infected with other persistent viruses. These data uncovered an eomesodermin-driven CD4 T cell program that is continuously suppressed by TGF-β signaling. During chronic viral infection, this program limits CD4 T cell responses while maintaining CD4 T helper cell identity.
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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.