ArticleCell host & microbe2015
PD-1 Co-inhibitory and OX40 Co-stimulatory Crosstalk Regulates Helper T Cell Differentiation and Anti-Plasmodium Humoral Immunity.
Article in Cell host & microbe, 2015. 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, 107 citations in OpenAlex.
- A CD40-OX40 co-stimulatory circuit orchestrates protective CD4Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
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- T follicular helper cell development during malaria.Current opinion in immunology · 2025Review
- Sindbis Virus Platform Provides an Oncolytic-Virus-Mediated and Immunotherapeutic Strategy to Overcome the Challenging Microenvironment of Pancreatic Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Systemic 4-1BB stimulation augments extrafollicular memory B cell formation and recall responses during Plasmodium infection.Cell reports · 2025Article
- Targeting T-Cell Activation for Malaria Immunotherapy: Scoping Review.Pathogens (Basel, Switzerland) · 2025Article
- Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.PLoS pathogens · 2025Review
- Synergistic blockade of TIGIT and PD-L1 increases type-1 inflammation and improves parasite control during murine blood-stageInfection and immunity · 2024Article
- ATG5-regulated CCL2/MCP-1 production in myeloid cells selectively modulates anti-malarial CD4Autophagy · 2024Article
- IL-15 Complex-Induced IL-10 Enhances Plasmodium-specific CD4+ T Follicular Helper Differentiation and Antibody Production.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Sindbis Virus Vaccine Platform: A Promising Oncolytic Virus-Mediated Approach for Ovarian Cancer Treatment.International journal of molecular sciences · 2024Review
- Decoupling FcRn and tumor contributions to elevated immune checkpoint inhibitor clearance in cancer cachexia.Pharmacological research · 2024Article
- The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8Cellular & molecular immunology · 2023Article
- Channeling the Natural Properties of Sindbis Alphavirus for Targeted Tumor Therapy.International journal of molecular sciences · 2023Review
- The Complexity of Interferon Signaling in Host Defense against Protozoan Parasite Infection.Pathogens (Basel, Switzerland) · 2023Review
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- Review
- B cell-intrinsic TBK1 is essential for germinal center formation during infection and vaccination in mice.The Journal of experimental medicine · 2022Article
- Providing a Helping Hand: Metabolic Regulation of T Follicular Helper Cells and Their Association With Disease.Frontiers in immunology · 2022Review
- Immunosuppression in Malaria: DoPathogens (Basel, Switzerland) · 2021Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The differentiation and protective capacity of Plasmodium-specific T cells are regulated by both positive and negative signals during malaria, but the molecular and cellular details remain poorly defined. Here we show that malaria patients and Plasmodium-infected rodents exhibit atypical expression of the co-stimulatory receptor OX40 on CD4 T cells and that therapeutic enhancement of OX40 signaling enhances helper CD4 T cell activity, humoral immunity, and parasite clearance in rodents. However, these beneficial effects of OX40 signaling are abrogated following coordinate blockade of PD-1 co-inhibitory pathways, which are also upregulated during malaria and associated with elevated parasitemia. Co-administration of biologics blocking PD-1 and promoting OX40 signaling induces excessive interferon-gamma that directly limits helper T cell-mediated support of humoral immunity and decreases parasite control. Our results show that targeting OX40 can enhance Plasmodium control and that crosstalk between co-inhibitory and co-stimulatory pathways in pathogen-specific CD4 T cells can impact pathogen clearance.
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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.