2000 Fiscal Year Annual Research Report

慢性活動性EBウイルス感染症とEBウイルス関連リンパ増殖症におけるT細胞の解析

Research Project

Project/Area Number	11670766
Research Institution	Kyushu University
Principal Investigator	大賀正一九州大学, 医学部・附属病院, 講師 (60233053)
Co-Investigator(Kenkyū-buntansha)	野村明彦九州大学, 医学部・附属病院, 助手 (00325531)
Keywords	慢性活動性EBウイルス感染症 / EBV-DNA / リンパ増殖性疾患 / サイトカイン / Th1 / Th2
Research Abstract	伝染性単核症(IM)の原因であるEpstein-Barrウイルス(EBV)は、免疫不全時に再活性化しB細胞リンパ腫/リンパ増殖性疾患(LPD)を、またT/NK細胞に感染して慢性活動性EBV感染症(CAEBV)や血球貪食症候群(HLH)などのリンパ網内系疾患を発症する。EBVがT細胞に感染したCAEBVやHLHは予後不良なEBV^+T-cell LPDである。私たちはCAEBV患児のT細胞活性化とoligoclonal増殖を明らかにし、活性化T細胞にEBVコピー数が多いこと、この細胞群のサイトカイン発現に異常のあることを明らかにした。このことはCAEBVにおける活性化T細胞の増殖が反応性というより、腫瘍化段階(clonal evolution)である可能性を示唆する。また、移植後LPDの発症予測に末梢血のEBV-DNA定量が有用であることも明らかにした。 1)CAEBV-T細胞におけるEBV量とサイトカイン発現患児の末梢血よりcDNAを作成して、T細胞抗原受容体Vβ,Jβ領域遺伝子を用いたinverse PCR法により、T細胞レパートアを解析しoligoclonal増殖を明らかにした。このT細胞をCell Sorter(EPICS-XL)によりHLA-DR陽性(活性化)と陰性(非活性化)群に分画しDNAとRNA(cDNA)を作成した。DNAを用いてEBV-DNAの、cDNAを用いてサイトカインmRNAの発現量をreal-time PCR(TaqMan)により定量した。活性化T細胞はEBV量が多く、Th1(IFNγ,IL-2)/Th2(IL-10,TGF-β)いずれのサイトカインも高発現していた。 2)EBV^+T/B-LPDにおけるEBV-DNAモニタリングの有用性 EBV-DNA定量(全血)が移植後B-LPDおよびCAEBV(T-LPD)の発症と病勢の指標になることを証明した。

Research Products
(32 results)

All Other

All Publications (32 results)

[Publications] Ohga S,Kubo E,Nomura A, et al.: "Quantitative monitoring of circulating Epstein-Barr virus DNA for predicting the development of posttransplant lymphoproliferative disease"Int J Haematol. (in press). (2001)
[Publications] Takada H,Nomura A,Ohga S,Hara T: "IL-18 in hemophagocytic lymphohistiocytosis"Leuk & Lymphoma. (in press). (2001)
[Publications] Ohga S,Nomura A,Takada H, et al.: "Epstein-Barr virus (EBV) load and cytokine gene expression in activated T cells of chronic active EBV infection"J Infect Dis. 183. 1-7 (2001)
[Publications] Honda K,Ohga S,Takada H, et al.: "Neuron specific enolase in hemophagocytic lymphohistiocytosis : a potential indicator for macrophage activation?"Int J Hematol. 72. 55-60 (2000)
[Publications] Honda K,Takada H,Nagatoshi Y,Akazawa K,Ohga S, et al.: "Thymus-independent expansion of T lymphocytes in children after allogeneic bone marrow transplantation"Bone Marrow Transplant. 25. 647-652 (2000)
[Publications] Mizuno Y,Takada H,Uragami K,Ihara K,Kira R,Ryutaro Kira,Suminoe A,Ohga S, et al.: "Neurotropin-3 levels in cerebrospinal fluid from children with bacterial meningitis, viral meningitis, or encephalitis"J Child Neurol. 15. 19-21 (2000)
[Publications] Ohga S,Kimura N,Takada H, et al.: "Restricted diversification of T-cells in chronic active Epstein-Barr virus infection : Potential inclination to T-lymphoproliferative disease"Am J Hematol. 61. 26-33 (1999)
[Publications] Ohshima K,Suzumiya J,Sugihara M,Nagafuchi S,Ohga S, et al.: "CD95 (Fas) ligand expression of Epstein-Barr virus (EBV)-infected lymphocytes : a possible mechanism of immune evasion in chronic active EBV infection"Pathol International. 49. 9-13 (1999)
[Publications] Takada H,Ohga S,Mizuno Y, et al.: "Oversecretion of interleukin 18 in hemophagocytic lymphohistiocytosis : a novel marker of disease activity"Br J Hematol. 10. 182-189 (1999)
[Publications] Ohga,Okada K,Ueda K, et al.: "Cerebospinal fluid cytokine levels and dexamethasone therapy in bacterial meningitis"J Infect. 39. 55-60 (1999)
[Publications] Kaiiwara M.,Nonovama S.,Eguchi M.,Morio T.,Imai K.,Okawa H.,Kaneko M.,Sako M.,Ohga S. et al.: "WASP is involved in proliferation and differentiation of human haematopoietic progenitors in vitro"Br J Haematol. 107. 254-262 (1999)
[Publications] Ohga S,Matsumoto N,Takada H,Nomura A, et al.: "Progressive vascular calcification in autoimmune polyglandular syndrome type I"Pediatric Radiology. (in press). (2001)
[Publications] Ohga S,Nomura A,Takada H, et al.: "Expansion of trisomy 8 and Sweet syndrome in a prolonged course of childhood aplastic anemia"J Pediatr Hematol/Oncol. (in press). (2001)
[Publications] Yamaguchi T,Ihara K,Matsumoto T,Tsutsumi Y,Nomura A,Ohga S,Hara T: "Inflammatory bowel disease in glycogen storage disease type Ib : a case report and literature review"Inflamm Bowel Dis. (in press). (2001)
[Publications] Ohga S,Kanaya Y,Maki H, et al.: "Epstein-Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond-Blackfan anemia"Bone Marrow Transplant. 25. 209-212 (2000)
[Publications] Nomura A,Ohga S,Asaka Y, et al.: "Pneumocystis carinii pneumonia in Diamond-Blackfan anemia : the necessity of chemoprophylaxis for young infant"Int J Pediatr Hematol/Oncol. 7. 7-11 (2000)
[Publications] Ohga S,Ryu A,Nagatomo T, et al.: "Inflammatory Bowel Disease in Anhidrotic Ectodermal Dysplasia : the lethal complication in two cases"Am J Gastroenterol. 95. 3651-3652 (2000)
[Publications] Kira R,Ohga S,Takada H, et al.: "MR choroid plexus sign of iron overload in secondary hemochromatosis"Neurology. 55. 1340 (2000)
[Publications] Ohga S,Takada H,Honda K, et al.: "Central nervous system T-lymphoproliferative disorder in chronic active Epstein-Barr virus infection"J Pediatr Hematol/Oncol. 21. 42-46 (1999)
[Publications] Nagatomo T,Ohga S,Saito M, et al.: "Streptococcus intermedius-brain abscess in chronic granulomatous disease"Eur J Pediatr. 158. 872-873 (1999)
[Publications] Sakai Y,Nakayama H,Matsuzaki A,Nagatoshi Y,Suminoe A,Honda K,Inamitsu T,Ohga S, et al.: "Trisomy 10 in a child with acute nonlymphocytic leukemia followed by relapse with a different clone"Cancer Genet Cytogenet. 115. 47-51 (1999)
[Publications] 伊野波論,稲村孝紀,大賀正一,原寿郎,福井仁士: "中枢神経系に浸潤したTリンパ球増殖性疾患(T-cell lymphoproliferative disorder)の2例"脳神経外科. 28. 435-439 (2000)
[Publications] 西尾俊嗣,森岡隆人,石原信一郎,大賀正一,三原太,福井仁士: "乳児頭蓋骨に発生したLangerhans cell histiocytosisの1例"臨床放射線. 45. 403-407 (2000)
[Publications] 大賀正一: "特集:SIRSとARDS-新しい炎症論と臨床-1.SIRS基礎2.SIRSの病態生理"サイトカイン""小児内科. 32. 1131-1136 (2000)
[Publications] 大賀正一: "小児の治療指針続発性免疫不全症"小児科診療. 62. 122-125 (2000)
[Publications] 高田英俊,野村明彦,大賀正一,中山英樹,石井直人,原寿郎: "低出生体重児に対する造血幹細胞移植"小児科. 41. 675-681 (2000)
[Publications] 大賀正一: "神経系感染症と進歩とその周辺:細菌性髄膜炎のデキサメサゾン療法とサイトカイン"神経研究の進歩. 43. 35-43 (1999)
[Publications] 大賀正一: "小児がん小児がん診療における感染症対策"小児科診療Q&A. 28:1733. 2-7 (1999)
[Publications] 大賀正一: ""感染とこども"ベッドサイドの小児の診かた第3版"南山堂(印刷中). (2001)
[Publications] 大賀正一,稲葉頌一: ""II.新生児の輸血D顆粒球輸血"小児輸血療法-安全で有効な輸血のために-"南江堂(印刷中). (2001)
[Publications] Ohga S,Takada H,Nomura A,Nagano M,Kimura N,Hara T: ""T-cell repertoire in chronic active Epstein-Barr virus infection : aberrant T cell expansions of intra-and extra-thymic lineages" Molecular and Genetic Approaches to Diseases-Immunology, Hematology, Oncology-N.Niho, editor"Kyushu University Press. 105-117 (1998)
[Publications] Takada H,Nomura A,Ohga S,Nakayama H,Hara T: ""Hematopoietic stem cell transplantation for premature infants : a possible application to fetuses" Proceedings, The 10^<th> Fukuoka International Symposium Perinatal Meeting"Maternity and Perinatal Care Unit Kyushu University Hospital. 1-10 (1999)

2000 Fiscal Year Annual Research Report

慢性活動性EBウイルス感染症とEBウイルス関連リンパ増殖症におけるT細胞の解析

Principal Investigator

大賀 正一 九州大学, 医学部・附属病院, 講師 (60233053)

Research Products

[Publications] Ohga S,Kubo E,Nomura A, et al.: "Quantitative monitoring of circulating Epstein-Barr virus DNA for predicting the development of posttransplant lymphoproliferative disease"Int J Haematol. (in press). (2001)

[Publications] Takada H,Nomura A,Ohga S,Hara T: "IL-18 in hemophagocytic lymphohistiocytosis"Leuk & Lymphoma. (in press). (2001)

[Publications] Ohga S,Nomura A,Takada H, et al.: "Epstein-Barr virus (EBV) load and cytokine gene expression in activated T cells of chronic active EBV infection"J Infect Dis. 183. 1-7 (2001)

[Publications] Honda K,Ohga S,Takada H, et al.: "Neuron specific enolase in hemophagocytic lymphohistiocytosis : a potential indicator for macrophage activation?"Int J Hematol. 72. 55-60 (2000)

[Publications] Honda K,Takada H,Nagatoshi Y,Akazawa K,Ohga S, et al.: "Thymus-independent expansion of T lymphocytes in children after allogeneic bone marrow transplantation"Bone Marrow Transplant. 25. 647-652 (2000)

[Publications] Mizuno Y,Takada H,Uragami K,Ihara K,Kira R,Ryutaro Kira,Suminoe A,Ohga S, et al.: "Neurotropin-3 levels in cerebrospinal fluid from children with bacterial meningitis, viral meningitis, or encephalitis"J Child Neurol. 15. 19-21 (2000)

[Publications] Ohga S,Kimura N,Takada H, et al.: "Restricted diversification of T-cells in chronic active Epstein-Barr virus infection : Potential inclination to T-lymphoproliferative disease"Am J Hematol. 61. 26-33 (1999)

[Publications] Ohshima K,Suzumiya J,Sugihara M,Nagafuchi S,Ohga S, et al.: "CD95 (Fas) ligand expression of Epstein-Barr virus (EBV)-infected lymphocytes : a possible mechanism of immune evasion in chronic active EBV infection"Pathol International. 49. 9-13 (1999)

[Publications] Takada H,Ohga S,Mizuno Y, et al.: "Oversecretion of interleukin 18 in hemophagocytic lymphohistiocytosis : a novel marker of disease activity"Br J Hematol. 10. 182-189 (1999)

[Publications] Ohga,Okada K,Ueda K, et al.: "Cerebospinal fluid cytokine levels and dexamethasone therapy in bacterial meningitis"J Infect. 39. 55-60 (1999)

[Publications] Kaiiwara M.,Nonovama S.,Eguchi M.,Morio T.,Imai K.,Okawa H.,Kaneko M.,Sako M.,Ohga S. et al.: "WASP is involved in proliferation and differentiation of human haematopoietic progenitors in vitro"Br J Haematol. 107. 254-262 (1999)

[Publications] Ohga S,Matsumoto N,Takada H,Nomura A, et al.: "Progressive vascular calcification in autoimmune polyglandular syndrome type I"Pediatric Radiology. (in press). (2001)

[Publications] Ohga S,Nomura A,Takada H, et al.: "Expansion of trisomy 8 and Sweet syndrome in a prolonged course of childhood aplastic anemia"J Pediatr Hematol/Oncol. (in press). (2001)

[Publications] Yamaguchi T,Ihara K,Matsumoto T,Tsutsumi Y,Nomura A,Ohga S,Hara T: "Inflammatory bowel disease in glycogen storage disease type Ib : a case report and literature review"Inflamm Bowel Dis. (in press). (2001)

[Publications] Ohga S,Kanaya Y,Maki H, et al.: "Epstein-Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond-Blackfan anemia"Bone Marrow Transplant. 25. 209-212 (2000)

[Publications] Nomura A,Ohga S,Asaka Y, et al.: "Pneumocystis carinii pneumonia in Diamond-Blackfan anemia : the necessity of chemoprophylaxis for young infant"Int J Pediatr Hematol/Oncol. 7. 7-11 (2000)

[Publications] Ohga S,Ryu A,Nagatomo T, et al.: "Inflammatory Bowel Disease in Anhidrotic Ectodermal Dysplasia : the lethal complication in two cases"Am J Gastroenterol. 95. 3651-3652 (2000)

[Publications] Kira R,Ohga S,Takada H, et al.: "MR choroid plexus sign of iron overload in secondary hemochromatosis"Neurology. 55. 1340 (2000)

[Publications] Ohga S,Takada H,Honda K, et al.: "Central nervous system T-lymphoproliferative disorder in chronic active Epstein-Barr virus infection"J Pediatr Hematol/Oncol. 21. 42-46 (1999)

[Publications] Nagatomo T,Ohga S,Saito M, et al.: "Streptococcus intermedius-brain abscess in chronic granulomatous disease"Eur J Pediatr. 158. 872-873 (1999)

[Publications] Sakai Y,Nakayama H,Matsuzaki A,Nagatoshi Y,Suminoe A,Honda K,Inamitsu T,Ohga S, et al.: "Trisomy 10 in a child with acute nonlymphocytic leukemia followed by relapse with a different clone"Cancer Genet Cytogenet. 115. 47-51 (1999)

[Publications] 伊野波論,稲村孝紀,大賀正一,原寿郎,福井仁士: "中枢神経系に浸潤したTリンパ球増殖性疾患(T-cell lymphoproliferative disorder)の2例"脳神経外科. 28. 435-439 (2000)

[Publications] 西尾俊嗣,森岡隆人,石原信一郎,大賀正一,三原太,福井仁士: "乳児頭蓋骨に発生したLangerhans cell histiocytosisの1例"臨床放射線. 45. 403-407 (2000)

[Publications] 大賀正一: "特集:SIRSとARDS-新しい炎症論と臨床-1.SIRS基礎2.SIRSの病態生理"サイトカイン""小児内科. 32. 1131-1136 (2000)

[Publications] 大賀正一: "小児の治療指針 続発性免疫不全症"小児科診療. 62. 122-125 (2000)

[Publications] 高田英俊,野村明彦,大賀正一,中山英樹,石井直人,原寿郎: "低出生体重児に対する造血幹細胞移植"小児科. 41. 675-681 (2000)

[Publications] 大賀正一: "神経系感染症と進歩とその周辺:細菌性髄膜炎のデキサメサゾン療法とサイトカイン"神経研究の進歩. 43. 35-43 (1999)

[Publications] 大賀正一: "小児がん 小児がん診療における感染症対策"小児科診療Q&A. 28:1733. 2-7 (1999)

[Publications] 大賀正一: ""感染とこども"ベッドサイドの小児の診かた 第3版"南山堂(印刷中). (2001)

[Publications] 大賀正一,稲葉頌一: ""II.新生児の輸血D顆粒球輸血"小児輸血療法-安全で有効な輸血のために-"南江堂(印刷中). (2001)

大賀正一九州大学, 医学部・附属病院, 講師 (60233053)

[Publications] 大賀正一: "小児の治療指針続発性免疫不全症"小児科診療. 62. 122-125 (2000)

[Publications] 大賀正一: "小児がん小児がん診療における感染症対策"小児科診療Q&A. 28:1733. 2-7 (1999)

[Publications] 大賀正一: ""感染とこども"ベッドサイドの小児の診かた第3版"南山堂(印刷中). (2001)