ArticlePLoS pathogens2014
Virus and autoantigen-specific CD4+ T cells are key effectors in a SCID mouse model of EBV-associated post-transplant lymphoproliferative disorders.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions.Frontiers in immunology · 2025Article
- Evaluation of novel Epstein-Barr virus-derived antigen formulations for monitoring virus-specific T cells in pediatric patients with infectious mononucleosis.Virology journal · 2024Article
- Editorial: EBV-induced T cell immunity in cancers.Frontiers in immunology · 2024Article
- EBV-induced T-cell responses in EBV-specific and nonspecific cancers.Frontiers in immunology · 2023Review
- Facts and Hopes in the Relationship of EBV with Cancer Immunity and Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
- Reconstitution of EBV-directed T cell immunity by adoptive transfer of peptide-stimulated T cells in a patient after allogeneic stem cell transplantation for AITL.PLoS pathogens · 2022Article
- Review
- The Role of Lytic Infection for Lymphomagenesis of Human γ-Herpesviruses.Frontiers in cellular and infection microbiology · 2021Review
- The Epstein-Barr Virus Major Tegument Protein BNRF1 Is a Common Target of Cytotoxic CD4Journal of virology · 2020Article
- Review
- Tumor Microenvironment Conditioning by Abortive Lytic Replication of Oncogenic γ-Herpesviruses.Advances in experimental medicine and biology · 2020Review
- Probing Reconstituted Human Immune Systems in Mice With Oncogenic γ-Herpesvirus Infections.Frontiers in immunology · 2020Review
- Review
- Defective Epstein-Barr virus in chronic active infection and haematological malignancy.Nature microbiology · 2019Article
- Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice.PLoS pathogens · 2018Article
- Signaling by the Epstein-Barr virus LMP1 protein induces potent cytotoxic CD4Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Emergence of CD4+ and CD8+ Polyfunctional T Cell Responses Against Immunodominant Lytic and Latent EBV Antigens in Children With Primary EBV Infection.Frontiers in microbiology · 2018Article
- Human γ-Herpesvirus Infection, Tumorigenesis, and Immune Control in Mice with Reconstituted Human Immune System Components.Frontiers in immunology · 2018Review
- Immune control of oncogenic γ-herpesviruses.Current opinion in virology · 2015Review
- Adoptive T-Cell Immunotherapy.Current topics in microbiology and immunology · 2015Review
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyclonal Epstein-Barr virus (EBV)-infected B cell line (lymphoblastoid cell lines; LCL)-stimulated T-cell preparations have been successfully used to treat EBV-positive post-transplant lymphoproliferative disorders (PTLD) in transplant recipients, but function and specificity of the CD4+ component are still poorly defined. Here, we assessed the tumor-protective potential of different CD4+ T-cell specificities in a PTLD-SCID mouse model. Injection of different virus-specific CD4+ T-cell clones showed that single specificities were capable of prolonging mouse survival and that the degree of tumor protection directly correlated with recognition of target cells in vitro. Surprisingly, some CD4+ T-cell clones promoted tumor development, suggesting that besides antigen recognition, still elusive functional differences exist among virus-specific T cells. Of several EBV-specific CD4+ T-cell clones tested, those directed against virion antigens proved most tumor-protective. However, enriching these specificities in LCL-stimulated preparations conferred no additional survival benefit. Instead, CD4+ T cells specific for unknown, probably self-antigens were identified as principal antitumoral effectors in LCL-stimulated T-cell lines. These results indicate that virion and still unidentified cellular antigens are crucial targets of the CD4+ T-cell response in this preclinical PTLD-model and that enriching the corresponding T-cell specificities in therapeutic preparations may enhance their clinical efficacy. Moreover, the expression in several EBV-negative B-cell lymphoma cell lines implies that these putative autoantigen(s) might also qualify as targets for T-cell-based immunotherapy of virus-negative B cell malignancies.
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