The manufacture of the EBV-T/NK LPD model mouse and the study of the clinical condition expression mechanism
| Project/Area Number |
22590374
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
IMADOME Ken-ichi 独立行政法人国立成育医療研究センター, 母児感染研究部, 室長 (70392488)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 疾患モデル動物 / EBV / CAEBV / EBV-HLH / NOGマウス / HLH |
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| Research Abstract |
Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients’ PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rcnull strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Transplantation of individual immunophenotypic subsets isolated from patients’ PBMC as well as that of various combinations of these subsets revealed a critical role of CD4_+T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4_+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases.
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] Characterization of Epstein-Barr virus (EBV)-infected cells in EBV-associated hemophagocytic lymphohistiocytosis in two patients with X-linked lymphoproliferative syndrome type1 and 22012
Author(s)
Imadome K, Yang X, Wada T, Nishida N, Mukai T, Fujiwara M, Kawashima H, Kato F, Fujiwara S, Yachie A, Zhao X, Miyawaki T, Kanegane H.
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Journal Title
Herpesviridae.
Volume: 3(1)
Pages: 1-1
Related Report
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[Journal Article] Recurrence of chronic active epstein-barr virus infection from donor cells after achieving complete response through allogeneic bone marrow transplantation.2012
Author(s)
Arai A, Imadome K, Wang L, Wu N, Kurosu T, Wake A, Yamamoto H, Ota Y, Harigai M, Fujiwara S, Miura O.
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Journal Title
Intern Med.
Volume: 51(7)
Pages: 777-82
NAID
Related Report
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[Journal Article] Effective control of Epstein-Barr virus infection following pediatric liver transplantation by monitoring of viral DNA load and lymphocyte surface markers2012
Author(s)
Imadome K, Fukuda A, Kawano F, Imai Y, Ichikawa S, Mochizuki M, Shigeta T, Kakiuchi T, Sakamoto S, Kasahara M, Fujiwara S.
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Journal Title
Pediatr Transplant.
Pages: 1399-3046
Related Report
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[Journal Article] ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis2012
Author(s)
Iijima K, Yamada H, Miharu M, Imadome K, Miyagawa Y, Akimoto S, Kobayashi K, Okita H, Nakazawa A, Fujiwara S, Fujimoto J, Kiyokawa N.
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Journal Title
Eur J Immunol.
Volume: 42(12)
Issue: 12
Pages: 3405-3415
DOI
Related Report
Peer Reviewed
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[Journal Article] Successful treatment with rituximab and donor lymphocyte infusions for fulminant EBV-associated lymphoproliferative disease that developed 14 years after unrelated BMT2011
Author(s)
Kawaguchi T, Tsukamoto S, Ohwada C, Takeuchi M, Muto T, Tanaka S, Sakai S, Takeda Y, Abe D, Sakaida E, Shimizu N, Yokote K, Iseki T, Imadome K, Nakaseko C
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Journal Title
Bone Marrow Transplantation
Volume: 31
Pages: 1-3
Related Report
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[Journal Article] Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood2011
Author(s)
Ohga S , Ishimura M , Yoshimoto G , Miyamoto T , Takada H , Tanaka T , Ohshima K , Ogawa Y , Imadome K , Abe Y , Akashi K , Hara T
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Journal Title
J Clin. Virol.
Volume: 51(1)
Pages: 31-7
Related Report
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[Journal Article] Epstein-Barr Virus Induces 1 Erosive Arthritis in Humanized Mice2011
Author(s)
Kuwana Y, Takei M, Yajima M, Imadome K , Inomata K , Shiozaki M, Ikumi N, Nozaki N, Shiraiwa H, Kitamura N, Takeuchi J ,Sawada S, Yamamoto N, Shimizu N, Ito M, Fujiwara S
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Journal Title
PLoS One
Volume: 6(10)
Pages: 26630-26634
Related Report
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[Journal Article] Novel Mouse Xenograft Models Reveal a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells2011
Author(s)
Imadome K, Yajima M, Arai A, Nakazawa A, Kawano F, Ichikawa S, Shimizu N, Yamamoto N, Morio T, Ohga S, Nakamura H, Ito M, Miura O, Komano J, Fujiwara S
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Journal Title
PLoS Pathogens
Volume: 7(10)
Pages: 1002326-1002340
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[Presentation] Novel Mouse Xenograft Models of CAEBV and EBV-HLH Reveals a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells2011
Author(s)
Ken-Ichi Imadome, Misako Yajima, Ayako Arai, Atsuko Nakazawa, Norio Shimizu, Naoki Yamamoto, Tomohiro Morio, Shouichi Ohga, Mamoru Ito, Jun Komano, Shigeyoshi Fujiwara
Organizer
XV, International Congress of Virology
Place of Presentation
Sapporo
Related Report
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[Presentation] A xenotransplant model of chronic active Epstein-Barr virus infection by use of NOG mice2010
Author(s)
Ken-Ichi Imadome, Misako Yajima, Ayako Arai, Atsuko Nakagawa, Fuyuko Kawano, Sayumi Ichikawa, Osamu Miura, Mamoru Ito, Norio Shimizu, Naoki Yamamoto, Shigeyoshi Fujiwara
Organizer
The 14^<th> Biennial Conference of the International Association for Research on Epstein-Barr virus & Associated Diseases
Place of Presentation
UK
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