ArticleJournal of immunology (Baltimore, Md. : 1950)2011
CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation.
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 99 papers.
What it found
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Who cites it
99 citing papers in PubMed, 151 citations in OpenAlex.
- Reduced Plasmodium Parasite Burden Associates with CD38+ CD4+ T Cells Displaying Cytolytic Potential and Impaired IFN-γ Production.PLoS pathogens · 2016Trial
- Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Cytotoxic CD4+ T cells in cancer: an emerging target for next-generation anticancer immunotherapy?Journal for immunotherapy of cancer · 2025Review
- Single cell-resolved cellular, transcriptional, and epigenetic changes in mouse T cell populations linked to age-associated immune decline.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cytotoxic CD4Frontiers in immunology · 2025Article
- Differential effects of immobilized CCL21 and ICAM1 on TILs with distinct expansion properties.Frontiers in immunology · 2025Article
- TIL Therapy in Lung Cancer: Current Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Cytotoxic Programming of CD4+ T Cells Is Regulated by Opposing Actions of the Related Transcription Factors Eos and Aiolos.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Biomarkers for response to TIL therapy: a comprehensive review.Journal for immunotherapy of cancer · 2024Review
- Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation.The Journal of experimental medicine · 2024Article
- Article
- The role of CD4MedComm · 2023Review
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- Human CD4 cytotoxic T lymphocytes mediate potent tumor control in humanized immune system mice.Communications biology · 2023Article
- CD4Frontiers in immunology · 2023Article
- Cytotoxic CD4 T cells in the mucosa and in cancer.Frontiers in immunology · 2023Review
- Cytotoxic CD4Frontiers in immunology · 2023Review
- Adoptive tumor infiltrating lymphocytes cell therapy for cervical cancer.Human vaccines & immunotherapeutics · 2022Review
- Regulation of CD4 T Cell Responses by the Transcription Factor Eomesodermin.Biomolecules · 2022Review
- First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors.Journal for immunotherapy of cancer · 2022Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Cytotoxic CD4 Th1 cells are emerging as a therapeutically useful T cell lineage that can effectively target tumors, but until now the pathways that govern their differentiation have been poorly understood. We demonstrate that CD134 (OX40) costimulation programs naive self- and virus-reactive CD4 T cells to undergo in vivo differentiation into cytotoxic Th1 effectors. CD137 (4-1BB) costimulation maximized clonal expansion, and IL-2 was necessary for cytotoxic Th1 differentiation. Importantly, the T-box transcription factor Eomesodermin was critical for inducing the cytotoxic marker granzyme B. CD134 plus CD137 dual costimulation also imprinted a cytotoxic phenotype on bystanding CD4 T cells. Thus, to our knowledge, the current study identifies for the first time a specific costimulatory pathway and an intracellular mechanism relying on Eomesodermin that induces both Ag-specific and bystander cytotoxic CD4 Th1 cells. This mechanism might be therapeutically useful because CD134 plus CD137 dual costimulation induced CD4 T cell-dependent tumoricidal function in a mouse melanoma model.
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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.