CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals.
To clarify the mechanism for development of Epstein-Barr virus (EBV)-positive T- or NK-cell neoplasms, we focused on the costimulatory receptor CD137. We detected high expression of CD137 gene and its protein on EBV-positive T- or NK-cell lines as compared with EBV-negative cell lines. EBV-positive...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4237363?pdf=render |
| _version_ | 1819262725544476672 |
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| author | Mayumi Yoshimori Ken-Ichi Imadome Honami Komatsu Ludan Wang Yasunori Saitoh Shoji Yamaoka Tetsuya Fukuda Morito Kurata Takatoshi Koyama Norio Shimizu Shigeyoshi Fujiwara Osamu Miura Ayako Arai |
| author_facet | Mayumi Yoshimori Ken-Ichi Imadome Honami Komatsu Ludan Wang Yasunori Saitoh Shoji Yamaoka Tetsuya Fukuda Morito Kurata Takatoshi Koyama Norio Shimizu Shigeyoshi Fujiwara Osamu Miura Ayako Arai |
| author_sort | Mayumi Yoshimori |
| collection | DOAJ |
| description | To clarify the mechanism for development of Epstein-Barr virus (EBV)-positive T- or NK-cell neoplasms, we focused on the costimulatory receptor CD137. We detected high expression of CD137 gene and its protein on EBV-positive T- or NK-cell lines as compared with EBV-negative cell lines. EBV-positive cells from EBV-positive T- or NK-cell lymphoproliferative disorders (EBV-T/NK-LPDs) patients also had significantly higher CD137 gene expression than control cells from healthy donors. In the presence of IL-2, whose concentration in the serum of EBV-T/NK-LPDs was higher than that of healthy donors, CD137 protein expression was upregulated in the patients' cells whereas not in control cells from healthy donors. In vitro EBV infection of MOLT4 cells resulted in induction of endogenous CD137 expression. Transient expression of LMP1, which was enhanced by IL-2 in EBV-T/NK-LPDs cells, induced endogenous CD137 gene expression in T and NK-cell lines. In order to examine in vivo CD137 expression, we used EBV-T/NK-LPDs xenograft models generated by intravenous injection of patients' cells. We identified EBV-positive and CD8-positive T cells, as well as CD137 ligand-positive cells, in their tissue lesions. In addition, we detected CD137 expression on the EBV infected cells from the lesions of the models by immune-fluorescent staining. Finally, CD137 stimulation suppressed etoposide-induced cell death not only in the EBV-positive T- or NK-cell lines, but also in the patients' cells. These results indicate that upregulation of CD137 expression through LMP1 by EBV promotes cell survival in T or NK cells leading to development of EBV-positive T/NK-cell neoplasms. |
| first_indexed | 2024-12-23T20:02:16Z |
| format | Article |
| id | doaj.art-81f8fd19b23c44acb535d895ba46bfe1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:02:16Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-81f8fd19b23c44acb535d895ba46bfe12022-12-21T17:33:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11256410.1371/journal.pone.0112564CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals.Mayumi YoshimoriKen-Ichi ImadomeHonami KomatsuLudan WangYasunori SaitohShoji YamaokaTetsuya FukudaMorito KurataTakatoshi KoyamaNorio ShimizuShigeyoshi FujiwaraOsamu MiuraAyako AraiTo clarify the mechanism for development of Epstein-Barr virus (EBV)-positive T- or NK-cell neoplasms, we focused on the costimulatory receptor CD137. We detected high expression of CD137 gene and its protein on EBV-positive T- or NK-cell lines as compared with EBV-negative cell lines. EBV-positive cells from EBV-positive T- or NK-cell lymphoproliferative disorders (EBV-T/NK-LPDs) patients also had significantly higher CD137 gene expression than control cells from healthy donors. In the presence of IL-2, whose concentration in the serum of EBV-T/NK-LPDs was higher than that of healthy donors, CD137 protein expression was upregulated in the patients' cells whereas not in control cells from healthy donors. In vitro EBV infection of MOLT4 cells resulted in induction of endogenous CD137 expression. Transient expression of LMP1, which was enhanced by IL-2 in EBV-T/NK-LPDs cells, induced endogenous CD137 gene expression in T and NK-cell lines. In order to examine in vivo CD137 expression, we used EBV-T/NK-LPDs xenograft models generated by intravenous injection of patients' cells. We identified EBV-positive and CD8-positive T cells, as well as CD137 ligand-positive cells, in their tissue lesions. In addition, we detected CD137 expression on the EBV infected cells from the lesions of the models by immune-fluorescent staining. Finally, CD137 stimulation suppressed etoposide-induced cell death not only in the EBV-positive T- or NK-cell lines, but also in the patients' cells. These results indicate that upregulation of CD137 expression through LMP1 by EBV promotes cell survival in T or NK cells leading to development of EBV-positive T/NK-cell neoplasms.http://europepmc.org/articles/PMC4237363?pdf=render |
| spellingShingle | Mayumi Yoshimori Ken-Ichi Imadome Honami Komatsu Ludan Wang Yasunori Saitoh Shoji Yamaoka Tetsuya Fukuda Morito Kurata Takatoshi Koyama Norio Shimizu Shigeyoshi Fujiwara Osamu Miura Ayako Arai CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals. PLoS ONE |
| title | CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals. |
| title_full | CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals. |
| title_fullStr | CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals. |
| title_full_unstemmed | CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals. |
| title_short | CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals. |
| title_sort | cd137 expression is induced by epstein barr virus infection through lmp1 in t or nk cells and mediates survival promoting signals |
| url | http://europepmc.org/articles/PMC4237363?pdf=render |
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