| Project/Area Number |
14570190
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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 | Tottori University (2003)
Okayama University (2002) |
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Principal Investigator |
HAYASHI Kazuhiko Tottori University, Molecular Pathology, Professor, 医学部, 教授 (30180962)
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| Co-Investigator(Kenkyū-buntansha) |
OHARA Nobuya Okayama University, Pathology, Assistant Professor, 大学院・医歯学総合研究科, 講師 (90325100)
TAKAHATA Hiroyuki TOTTORI UNIVERSITY, Molecular Pathology, ASSISTANT, 医学部, 助手
山田 雅夫 岡山大学, 大学院・医歯学総合研究科, 教授 (40166731)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | EBV / Herpesvirus papio / Rabbit / hemophagocytic syndrome / T-cell / LPDs / HVP / ウサギ / 血球貪食症候群 / 治療 |
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| Research Abstract |
Epstein-Barr virus associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-
… More
ISH of immunomagnetic purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+ or CD79a+fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, andthymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2 dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVR infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Less
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