| Project/Area Number |
11670766
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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 |
Pediatrics
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| Research Institution | Kyushu University |
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Principal Investigator |
OHGA Shouichi Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Lecturer, 医学部・附属病院, 講師 (60233053)
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| Co-Investigator(Kenkyū-buntansha) |
NOMURA Akihiko Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Assistant Professor, 医学部・附属病院, 助手 (00325531)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | chronic active Epstein-Barr virus infection / EBV-DNA / lymphoproliferative diseases (disorders) / cytokine / T helper (Th) 1 / Th2 / 慢性活動性EBV感染症 / EBVウイルス量 / 細胞内サイトカイン |
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| Research Abstract |
Epstein-Barr virus (EBV), the causative agent of acute infectious mononucleosis (IM) leads to the persistent reactivation and the subsequent development of B-cell lymphoma/lymphoproliferative disease (LPD) in immunodeficient patients. This γ-herpes virus can infect T/NK cells and thus be associated with lymphoreticular diseases including chronic active EBV infection (CAEBV) and hemophagocytic lymphohistiocytosis (HLH). These conditions have now been classified into EBV^+T-cell LPD.The present study on CAEBV revealed the followings ; 1) T-cells are activated and expanded ologoclonally, 2) The activated T-cells carried increased copy number of EBV genome, 3) and expressed unbalanced high expression of cytokines. These results suggest that activated T-cells of CAEBV may represent the clonal evolution of malignancy, rather than the reactive condition against EBV infection. We also demonstrated the usefulness of quantitative monitoring of EBV-DNA in predicting the development of posttransplant LPD.
1) EBV load and cytokine expression in CAEBV T-cells
The inverse PCR methods using T-cell antigen receptor (TCR) Vβ/Jβ region genes revealed oligoclonal expansion of T-cells in CAEBV patients. T cells were fractionated into HLA-DR^+ or HLA-DR^-CD3^+ cells by a cell sorter (EPICS-XL), and DNA and cDNA were constructed from each population, respectively. EBV-DNA and cytokine mRNA were quantified by real-time PCR (TaqMan). CD3^+HLA-DR^+ cells contained higher copy numbers of virus than CD3^+HLA-DR^- cells. Quantitative PCR for cytokines indicated high expressions of Th1 (IFNγ, IL-2) and Th2 (IL-10, TGF-β) cytokines in activated T-cells.
2) Clinical usefulness of posttransplant EBV-DNA monitoring
EBV-DNA was sequentially quantified by real-time PCR in 12 patients after hematopoietic stem cell transplantation. Progressive increase of EBV-DNA indicated the development of posttransplant LPD.
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