7 results on '"Yasuda, Tomoharu"'
Search Results
2. Concomitant Cytotoxic Effector Differentiation of CD4 + and CD8 + T Cells in Response to EBV-Infected B Cells.
- Author
-
Tamura, Yumi, Yamane, Keita, Kawano, Yohei, Bullinger, Lars, Wirtz, Tristan, Weber, Timm, Sander, Sandrine, Ohki, Shun, Kitajima, Yasuo, Okada, Satoshi, Rajewsky, Klaus, and Yasuda, Tomoharu
- Subjects
FLOW cytometry ,B cells ,VIRAL proteins ,ANIMAL experimentation ,CARCINOGENESIS ,IMMUNE system ,PROTEOLYTIC enzymes ,GENE expression ,GENE expression profiling ,IMMUNITY ,T cells ,CELL lines ,EPSTEIN-Barr virus diseases ,CYTOTOXINS ,MICE - Abstract
Simple Summary: The Epstein–Barr virus (EBV) is a γ-herpes virus that primarily infects human B cells, and more than 90% of adults have experienced infection. EBV
+ B cells express several viral proteins, transmitting signals important for the transformation and tumorigenesis of the infected B cells. Immune surveillance by the host immune system is important to suppress such abnormal expansion of EBV-infected B cells. Here we found that both CD4+ T cells and CD8+ T cells show similar gene expression patterns relating to cytotoxicity towards EBV-infected B cells. EBV-specific cytotoxic CD4+ T cells markedly expressed T-bet, Granzyme B, and Perforin alongside killing activity, which could reflect mechanisms shared with cytotoxic CD8+ T cells. Our findings support the concept that, upon EBV and perhaps other viral infections, T cells of different subsets can be drawn into common pathways mediating immune surveillance through cytotoxicity. Most people infected by EBV acquire specific immunity, which then controls latent infection throughout their life. Immune surveillance of EBV-infected cells by cytotoxic CD4+ T cells has been recognized; however, the molecular mechanism of generating cytotoxic effector T cells of the CD4+ subset remains poorly understood. Here we compared phenotypic features and the transcriptome of EBV-specific effector-memory CD4+ T cells and CD8+ T cells in mice and found that both T cell types show cytotoxicity and, to our surprise, widely similar gene expression patterns relating to cytotoxicity. Similar to cytotoxic CD8+ T cells, EBV-specific cytotoxic CD4+ T cells from human peripheral blood expressed T-bet, Granzyme B, and Perforin and upregulated the degranulation marker, CD107a, immediately after restimulation. Furthermore, T-bet expression in cytotoxic CD4+ T cells was highly correlated with Granzyme B and Perforin expression at the protein level. Thus, differentiation of EBV-specific cytotoxic CD4+ T cells is possibly controlled by mechanisms shared by cytotoxic CD8+ T cells. T-bet-mediated transcriptional regulation may explain the similarity of cytotoxic effector differentiation between CD4+ T cells and CD8+ T cells, implicating that this differentiation pathway may be directed by environmental input rather than T cell subset. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
3. Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis
- Author
-
Sommermann, Thomas, Yasuda, Tomoharu, Ronen, Jonathan, Wirtz, Tristan, Weber, Timm, Sack, Ulrike, Caeser, Rebecca, Zhang, Jingwei, Li, Xun, Chu, Van Trung, Jauch, Anna, Unger, Kristian, Hodson, Daniel J, Akalin, Altuna, Rajewsky, Klaus, Sommermann, Thomas [0000-0003-2899-0256], Ronen, Jonathan [0000-0003-3980-6469], Weber, Timm [0000-0003-2079-842X], Hodson, Daniel J [0000-0001-6225-2033], and Apollo - University of Cambridge Repository
- Subjects
Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Lymphoma, B-Cell ,Plasma Cells ,Primary Cell Culture ,plasma cell differentiation ,Viral Matrix Proteins ,Mice ,Viral Proteins ,hemic and lymphatic diseases ,Cell Line, Tumor ,otorhinolaryngologic diseases ,Epstein-Barr virus ,Animals ,Humans ,LMP1 ,Mice, Knockout ,B cell lymphomagenesis ,Cell Differentiation ,EBNA ,Fibroblasts ,Cell Transformation, Viral ,DNA-Binding Proteins ,stomatognathic diseases ,Disease Models, Animal ,Epstein-Barr Virus Nuclear Antigens ,Trans-Activators - Abstract
Epstein-Barr virus (EBV) is a B cell transforming virus that causes B cell malignancies under conditions of immune suppression. EBV orchestrates B cell transformation through its latent membrane proteins (LMPs) and Epstein-Barr nuclear antigens (EBNAs). We here identify secondary mutations in mouse B cell lymphomas induced by LMP1, to predict and identify key functions of other EBV genes during transformation. We find aberrant activation of early B cell factor 1 (EBF1) to promote transformation of LMP1-expressing B cells by inhibiting their differentiation to plasma cells. EBV EBNA3A phenocopies EBF1 activities in LMP1-expressing B cells, promoting transformation while inhibiting differentiation. In cells expressing LMP1 together with LMP2A, EBNA3A only promotes lymphomagenesis when the EBNA2 target Myc is also overexpressed. Collectively, our data support a model where proproliferative activities of LMP1, LMP2A, and EBNA2 in combination with EBNA3A-mediated inhibition of terminal plasma cell differentiation critically control EBV-mediated B cell lymphomagenesis.
- Published
- 2020
4. How Should We Deal with Neoplastic Disease and Serious Infections Caused by Epstein–Barr Virus?
- Author
-
Yoshiyama, Hironori, Nanbo, Asuka, and Yasuda, Tomoharu
- Subjects
CARCINOGENESIS ,KILLER cells ,EPSTEIN-Barr virus ,CELL proliferation ,TUMORS ,HERPESVIRUSES ,EPSTEIN-Barr virus diseases ,DISEASE complications - Published
- 2023
- Full Text
- View/download PDF
5. Pathologically Relevant Mouse Models for Epstein–Barr Virus–Associated B Cell Lymphoma.
- Author
-
Huang, Shiyu and Yasuda, Tomoharu
- Subjects
B cells ,ANIMAL disease models ,LYMPHOMAS ,EPSTEIN-Barr virus ,IMMUNOSUPPRESSION ,MUSCLE tumors - Abstract
The Epstein–Barr virus (EBV) is endemic in humans and can efficiently transform infected B cells under some circumstances. If an EBV carrier experiences immune suppression, EBV
+ B cells can turn into lymphoblasts and exhibit growth expansion that may cause lymphoproliferative diseases which often develop into lymphoma. Our immune system conducts surveillance for EBV+ B cells in order to block spontaneous tumor formation. Here, we summarize the EBV products involved in tumorigenesis, EBV-associated lymphomas, and pathologically relevant mouse models. Preclinical mouse models for a range of EBV-associated diseases not only clear the path to new therapeutic approaches but also aid in our understanding of the nature of lymphomagenesis and immune surveillance. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
6. Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis
- Author
-
Sommermann, Thomas, Yasuda, Tomoharu, Ronen, Jonathan, Wirtz, Tristan, Weber, Timm, Sack, Ulrike, Caeser, Rebecca, Zhang, Jingwei, Li, Xun, Chu, Van Trung, Jauch, Anna, Unger, Kristian, Hodson, Daniel J, Akalin, Altuna, and Rajewsky, Klaus
- Subjects
Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Lymphoma, B-Cell ,Plasma Cells ,Primary Cell Culture ,plasma cell differentiation ,Viral Matrix Proteins ,Mice ,Viral Proteins ,hemic and lymphatic diseases ,Cell Line, Tumor ,otorhinolaryngologic diseases ,Epstein-Barr virus ,Animals ,Humans ,LMP1 ,Mice, Knockout ,B cell lymphomagenesis ,Cell Differentiation ,EBNA ,Fibroblasts ,Cell Transformation, Viral ,3. Good health ,DNA-Binding Proteins ,stomatognathic diseases ,Disease Models, Animal ,Epstein-Barr Virus Nuclear Antigens ,Trans-Activators - Abstract
Epstein-Barr virus (EBV) is a B cell transforming virus that causes B cell malignancies under conditions of immune suppression. EBV orchestrates B cell transformation through its latent membrane proteins (LMPs) and Epstein-Barr nuclear antigens (EBNAs). We here identify secondary mutations in mouse B cell lymphomas induced by LMP1, to predict and identify key functions of other EBV genes during transformation. We find aberrant activation of early B cell factor 1 (EBF1) to promote transformation of LMP1-expressing B cells by inhibiting their differentiation to plasma cells. EBV EBNA3A phenocopies EBF1 activities in LMP1-expressing B cells, promoting transformation while inhibiting differentiation. In cells expressing LMP1 together with LMP2A, EBNA3A only promotes lymphomagenesis when the EBNA2 target Myc is also overexpressed. Collectively, our data support a model where proproliferative activities of LMP1, LMP2A, and EBNA2 in combination with EBNA3A-mediated inhibition of terminal plasma cell differentiation critically control EBV-mediated B cell lymphomagenesis.
7. Immune Surveillance and Therapy of Lymphomas Driven by Epstein-Barr Virus Protein LMP1 in a Mouse Model
- Author
-
Zhang, Baochun, Kracker, Sven, Yasuda, Tomoharu, Casola, Stefano, Vanneman, Matthew, Hömig-Hölzel, Cornelia, Wang, Zhe, Derudder, Emmanuel, Li, Shuang, Chakraborty, Tirtha, Cotter, Shane E., Koyama, Shohei, Currie, Treeve, Freeman, Gordon J., Kutok, Jeffery L., Rodig, Scott J., Dranoff, Glenn, and Rajewsky, Klaus
- Subjects
- *
EPSTEIN-Barr virus , *LYMPHOMAS , *LABORATORY mice , *B cells , *CELL receptors , *IMMUNOSUPPRESSION - Abstract
Summary: B cells infected by Epstein-Barr virus (EBV), a transforming virus endemic in humans, are rapidly cleared by the immune system, but some cells harboring the virus persist for life. Under conditions of immunosuppression, EBV can spread from these cells and cause life-threatening pathologies. We have generated mice expressing the transforming EBV latent membrane protein 1 (LMP1), mimicking a constitutively active CD40 coreceptor, specifically in B cells. Like human EBV-infected cells, LMP1+ B cells were efficiently eliminated by T cells, and breaking immune surveillance resulted in rapid, fatal lymphoproliferation and lymphomagenesis. The lymphoma cells expressed ligands for a natural killer (NK) cell receptor, NKG2D, and could be targeted by an NKG2D-Fc fusion protein. These experiments indicate a central role for LMP1 in the surveillance and transformation of EBV-infected B cells in vivo, establish a preclinical model for B cell lymphomagenesis in immunosuppressed patients, and validate a new therapeutic approach. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.