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1991 Fiscal Year Final Research Report Summary

Analysis of Mechanisms underlying Autoantibody production in Chronic Graft-versus-host Reaction

Research Project

Project/Area Number 01570364
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionYokohama City University School of Medicine

Principal Investigator

AOKI Ichiro  Yokohama City University School of Medicine, Department of Pathology, Instructor, 医学部, 講師 (00184028)

Co-Investigator(Kenkyū-buntansha) NARITA Masahiro  Yokohama City University School of Medicine, First Department of Medicine, Assis, 医学部, 助手 (50218062)
Project Period (FY) 1989 – 1991
KeywordsGraft-versus-host reaction / B cell activation / Autoantibody / Glomerulonephrites / IgG / Ultrastructure / Interstitial pneumonia / Mouse
Research Abstract

Several series of the experiments were conducted to analyze the mechanisms underlying autoimmunity Induced by chronic graft-versus-host reaction (GVHR).
(1) ELISA spot assay was employed to investigate the mechanisms of autoantibody production by GVHR. Conventional antibody (ant-TNP, anti-OVA) producing cells were shown to be activated by GVHR as well as autoantibody (anti-DNA, iTA, etc) producing cells. Thus, It was suggested that autoantibody production might be associated with polyclonal B cell activation in chronic GVIIR.
(2) Electron microscopical examination on the glomerular lesion demonstrated electron dense deposits first In the mesangial matrix, then in the subepithellum compatible with Immune complex glomerulonephrltls. Subendothellal deposits were not observed. Immunofluorescent study revealed IgG deposition In the capillary wall and IgM in the mesanglum early In the process. Some glomerull showed segmental mesangiolysis, suggesting that altered mesangial cells have a role In … More the development of glomerular change, which together with rise In serum autoantibody titer suggest that autoantibodies promote the glomerular lesions In this model system.
(3) GVIIR was induced In BDF_1 and (BALB/cx A)F_1(CAF_1) murine recipients by Injection of their parental or B10. D2-derlved spleen cells. The lncridences of glomerulonephritis and autoantibody production were then correlated. All BDF_1 mice that received DBA/2 spleen cells (termed DBA/2->BDF_1) and 33% of CAF_1 mice that received BALB/c spleen cells (BALB/c->CAF_1) developed glomerulonephritis. However, In other combinations (B10. D2->BDF_1, A/J->CAF_1) no significant glomerular leslons were observed. Analysis of antibodies by ELISA has revealed that the groups with renal disease showed significant polyclonal elevaton of IgG-class antibodies, including autoantibodies (anti-DNA, anti-MRBC and NTA) and conventional antibody (antl-TNP-KLII). No significant IgG class antibody production was observed In the groups that did not develop glomerulonephritis. Thus, it was suggested that an IgM to IgG class switch is important In the development of glomerulonephritis In GVHR. Other factors appear to be involved. Only 33% of BALB/C->CAF_1 developed glomerulonephritis even though a level of IgG class antibody production was comparable to that observed In DBA/2->BDF_1 In which 100% showed severe glomerulonephritis.
(4) Myc and Raf gene expression was analysed and compared with B cell activity and cell kinetics. ELISA spot assay revealed transient B cell proliferation with a peak at 3 week after transfer. Mye and Raf genes showed the Increased expression wlth the peak at 3 weeks after transfer. This profile was consistent with that of B cell prollferation revealed by ELISA spot assay. Cell kinetics analysis revealed that proliferative cells In G2+M phase increased 4 weeks after transfer. Thus, the myc and raf activity has been considered to be correlated to the B cell activity. These oncogene activity Is considered to be correlated with abnormal lymphold cell proliferation from the lnvestigations on lymphold cell malignancy and spontaneous autoimmune model mouse. Since proliferative B cells In GVHR Is Intrinsically normal, the present findings seem to indicate In vivo evidence of Involvement of myc and raf gene In B cell proliferation.
(5) Microscopical examination revealed mononuclear cell Infiltration In pulmonary alveolar wall of DBA/2->BDF_1, suggesting the presence of mild degree of interstitial pneumonlae. Increase of lymphocytes and angotensin converting enzyme activity In bronchloalveolar lavage fluid was consistent with this notion. Pathological change in the lungs of DBA/2->BDF_1 was suggested to be a model of interstitial pneumonia. Less

  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Otani M,Aoki I,Misugi K,Hagiwara E and Aoki A.: "Glomerulonephritis in murine chronic graft-versus-host reaction." Journal of Clinical Electron Microscopy. 22. 5-6 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Daikaku M et al: "Incidence and titer of anti-rev antibody in HIV infection." AIDS.3. 755-756 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 青木 昭子,その他: "慢性GVH病マウスにおける血清抗体レベルおよび抗体産生細胞の比較" 日本免疫学会総会学術集会記録. 19. 463 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田中 俊一,その他: "Streptozocinによるマウス自己免疫性糖尿病発症の遺伝的調節" 日本免疫学会総会・学術集会記録. 19. 531 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 青木 一郎,その他: "GVHにおけるB細胞活性化とcーmyc遺伝子の発現" 分子病理研究会会誌. 2. 1 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 青木 一郎,奥田 研爾: "T細胞レセプタ-" 臨床検査. 33. 948-949 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aoki I,Otani M,Miyagi Y,Misugi K and Ishii N,: "The Effect of Cyclosporine on Allospecific Immune Response in vivo." Transplantation Proceedings. 22. 260-263 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishii N,Ishii H,Ono H,Horiuchi Y,Nakajima H and Aoki I.: "Effect of cyclosporin A on suppressor T cells" Journal of Dermatological Science. 1. 73-78 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishii N,Ishii H,Ono H,Horiuchi Y,Nakajima H and Aoki I.: "Genetic Control of Nickel Sulfate Delayed-Type Hypersensitivity." Jouranal of Investigative Dermatology. 94. 673-676 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka S et al.: "Genetic Control by I-A Subregion in H-2 Complex of Incidence of Streptozocin-Induced Autoimmune Diabetes in Mice." Diabetes.39. 1298-1304 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Otani M,Aoki I,Nakatani Y,Misugi K,Ehara M,Iwamoto and M,Fujiwara Y.: "Oberevation of PAM stained human renal biopsy specimen by scanning electron microscopy." Journal of Clinical Electron Microscopy. 23. 5-6 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishii N,Nakajima H,Aoki I,Shimoda N and Mori T.: "Genetic Control of Delayed Type Hypersensitivity of Mycobacterium Leprae Antigen." Japanese Journal of Leprosy. 59. 154-161 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 青木 一郎,その他: "移植片対宿主反応による自己免疫病.I.腎糸球体病変と自己抗体." 日本病理学会誌. 79. 281 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大谷 方子,その他: "移植片対宿主反応による自己免疫病.II.免疫複合体糸球体腎炎の微細形態." 日本病理学会誌. 79. 354 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 宮城 洋平,その他: "移植片対宿主反応による自己免疫病.III.B細胞活性化とcーmyc遺伝子の発現." 日本病理学会誌. 79. 219 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大谷 方子、その他: "乳児期早期における皮膚限局性組織球増殖症の2症例." 病理と臨床. 8. 1549-1553 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishii N,Nakajima H,Tanaka S,Aoki I,Ishii T and Shimoda N: "Prolongation of Murine Skin Graft Survival by Photoperesis." Yokohama Medical Bulletin. 41. 107-114 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishii N,Ishii H,Nakajima H,Aoki I and Shimoda N.: "Contact Sensitivity To Mercuric Chloride Is Associated With I-A Region In Mice." Journal of Dermatological Science. 2. 268-273 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大谷 方子,大野 伸一,青木 一郎,三杉 和章: "急速凍結・ディ-プエッチング法によるマウス慢性移植片対宿主反応における糸球体病変の超微形態学的研究" 横浜医学. 42. 685-691 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大谷 方子,長嶋 洋治,北條 晴人,中谷 行雄,青木 一郎,大秋 美治,三杉 和章.: "KlippleーFeil症候群を伴った胸椎のEnterogenous cystの1剖検例" 横浜医学. 42. 723-727 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 稲見 すま子,その他: "本邦HIVウィルス感染患者23例中の種々合成抗原定基に対する血中抗体価の検討." エイズジャ-ナル. 3. 222-224 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石ヶ坪 良明,その他: "慢性GVHDによる肺病変" 日本胸部疾患学会雑誌. 29. 224 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 青木 一郎,青木 昭子,大谷 方子,石ヶ坪 良明,大久保 隆男,三杉 和章,奥田 研爾.: "慢性GVHDにおける腎炎発症と抗体価" 日本免疫学会総会・学術集会記録. 21. 414 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大野 滋,その他: "慢性GVHDによる間質性肺病変" 日本免疫学会総会・学術集会記録. 21. 413 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大谷 方子,三杉 和章,江原 美智子,青木 一郎: "PAM染色試料における賢生検田走査電顕像" 腎と透析. 32. 253-257 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aoki I et al: "A Correlation between IgG Glass Antibody and Glomerulonephritis in the Murine Chronic Graft-Versus-Host reaction" Clinical Immunology and Immunopathology. (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Otani M,Aoki I,Miyagi Y,Misugi K,Aoki A and Ishigatsubo Y.: "Glomerulonephritis Induced by Chronic Graft-Versus-Host Reaction" Acta Pathoogica Japonica. (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Otani M,Ohno S,Aoki I,Misugi K,Nakazawa K and Shigematsu H.: "Three-Dimensional Study of Glomerular Lesion in Murine Chronic Graft-Versus-Host Reaction by Quicl-Freezing and Deep-Etching Method." Nephron. (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aoki A et al: "Polyclonal B cell Activation and Antigen SpecificStimulation in Mice with Chronic Graft-Versus-Host Reaction"

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Otani M, Aoki I, Misugi K, Hagiwara E and Aoki A.: "Glomerulonephritis in murine chronic graft-versus-host reaction." Clin. Electron Microscopy. 22. 5-6 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Dairaku M, Tsuchie H, Ushijima H, Aoki I, Okuda K, Honda M, Ikegami N, Hachimori K, Matsuda J and Kitamura T.: "Incidence and titer of anti-rev antibody in HIV infection." AIDS.3. 755-756 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki A, Ishigatsubo Y, Hagiwara E, Shirai A, Narita M, Matsunaga K, Tani K, Okubo T, Otani M, Miyagi Y, Aoki I, Misugi K, Okuda K.: "Comparative study of serum antibody titer and antibody-producing cells in chronic GVHD (graft-versus-host disease) mice." Proc. Jpn. Soc. Immunol.19. 463 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka S, Nakajima S, Ishihara M, Yamakawa T, Inoue S, Takamura Y, Aoki I, Okuda K.: "Genetic control of low-dose streptozocin induced autoimmune diabetes." Proc. Jpn. Soc. Immunol.19. 531 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki I, Miyagi Y, Otani M, Misugi K, Aoki A, Hagiwara E, Ishigatsubo Y.: "B cell activation and myc gene expression in graft-versus-host reaction." Tr. Soc. Mol. Pathol. Jpn.2. 1

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki I and Okuda K.: "T cell receptor." Rinsho-Kensa. 33. 948-949 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki I, Otani M, Miyagi Y, Misugi K and Ishii N.: "The effect of Cyclosporine on Allospecific Immune Response in vivo." Transplantation Proceedings. 22. 260-263 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii N, Ishii H, Ono H, Horiuchi Y, Nakajima H and Aoki I.: "Effect of cyclosporin A on suppressor T cells." J. Dermatological Science. 1. 73-78 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii N, Ishii H, Ono H, Horiuchi Y, Nakajima H and Aoki I.: "Genetic control of Nickel Sulfate Delayed-Type Hypersensitivity." J Invet. Dermatol.94. 673-676 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka S. Nakajima S, Inoue S, Takamura Y, Aoki I and Okuda K.: "Genetic Control by I-A subregion in H-2 Complex of Incidence of Streptozocin-Induced Autoimmune Diabetes in Mice." Diabetes.39. 1298-1304 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otani M, Aoki I, Nakatani Y, Misugi K, Ehara M, Iwamoto M, Fujiwara Y.: "Obesevation of PAM stained human renal biopsy specimen by scanning electron microscopy." J. Clin Electron Microscopy. 23. 5-6 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii N, Nakajima H, Aoki I, shimoda N, Mori T.: "Genetic Control of Delayed Type Hypersensitivity to Mycobacterium Leprae Antigen." Jap. J Leprosy. 59. 154-161 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki I, Otani M. Miyagi Y, Misugi K, Hagiwara E, Aoki A, and Ishigatsubo Y.: "Autoimmune disease induced by chronic Graft-versus-host disease, I. Glomerular lesion and autoantibodies." Tr. Soc. Pathol. Jpn.79. 281 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otani M, Aoki I, Miyagi Y, Misugi K, Hagiwara E, Aoki A, and Ishigatsubo Y.: "Autoimmune Disease induced by chronic Graft-versus-host disease. II. Ultrastructure of Immune complex glomerulonephritis" Tr. Soc. Pathol. Jpn.79. 354 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyagi Y, Aoki I, Otani M, Misugi K, Hagiwara E, Aoki A, and Ishigatsubo Y.: "Autoimmune disease induced by chronic graft-versus-host disease. III. B cell activation and c-myc expression" Tr. Soc. Pathol. Jpn.79. 219 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otani M, Ohaki Y, Aoki I, Misugi K and Hara M: "Two cases of cutaneous histiocyte proliferative disorders in early infancy." Byouri to Rinsho. 8. 1549-1553 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii N, Nakajima H, Tanaka S, Aoki I, Ishii T and Shimoda N: "Prolongation of Murine Skin Graft Survival by Photoperesis." Yokohama Med. Bull.41. 107-114 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii N, Ishii H, Nakajima H, Aoki I and Shimoda N.: "Contact Sensitivity To Mercuric Chloride Is Associated With I-A Region In Mice." J. Dermatol. Sci.2. 268-273 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otani M, Ohno S, Aoki I and Misugi K.: "Ultrastructural Study of glomeruli in murine chronic graft-versus-host reaction by quick -freezing and deep-etching method." Yokohoama Igaku. 42. 685-691 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otani M, Nagashima Y, Hojo H, Nakatani Y, Aoki I, Ohaki Y, Misugi K.: "Enterogenous cyst of the upper thracic vertebra with Klippel-Feil syndrome." Yokohoama Igaku. 42. 723-727 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inami S, Taniguchi N, Isibashi K, Nagao H, Aoki I, Ishii N, Yamakawa T, Tanaka S, Ushijima H, Okuda K.: "Serum Antibody titers against synthetic peptides in 23 cases of HIV infectious patients in Japan." AIDS Journal. 3. 222-224 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishigatsubo Y. Aoki A, Hagiwara E, Ohno S, Ueda A, Okubo T, Nakatani Y and Aoki I.: "Pulmonary lesion in chronic graft-versus-host disease." Jpn J Thoracic Disease. 29. 224 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki I, Aoki A, Otani M, Ishigatsubo Y, Okubo T, Misugi K, Okuda K.: "Glomerulonephritis and antibody production in chronic grafy-versus-host disease." Proc. Soc. Jpn. Immunol.21. 414 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohno S, Ishigatsubo Y, Aoki A, Hagiwara E, Ueda A, Soga T, Tani K, Aoki I, Misugi K, Kawakami R, Takenaka T, Okubo T.: "Interstitial pulmonary lesion inchronic GVHD." Proc. Soc. Jpn. Immunol.21. 414 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otani M, Kazuaki M, Ehara M and Aoki I: "Scanning electron microscopy examination on PAM stained renal biopsy." Jin To Tohseki. 32. 253-257 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki I, Aoki A, Otani M, Miyagi Y, Misugi M, Ishii N, Hagiwara E, Tani K, Okubo T and Ishigatsubo Y.: "A Correlation between IgG Class Antibody and Glomerulonephritis in the Murine Chronic Graft-Versus-Host reaction." Clinical Immunology and Immunopathology. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otani M, Aoki I, Miyagi Y, Misugi K, Aoki A and Ishigatsubo Y.: "Glomerulonephritis Induced by Chronic Graft-Versus-Host Reaction." Acta Pathol Jap. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otani M, Ohno S, Aoki I, Misugi K, Nakazawa K and Shigematsu H.: "Three-Dimensional Study of Glomerular Lesion in Murine Chronic Graft-Versus-Host Reaction by Quick-Freezing and Deep-Etching Method." Nephron. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki A, Ishigatsubo Y, Hagiwara E, Shirai A, Tani K, Maruta A, Otani M, Aoki I, Misugi Y and Okubo T.: "Polyclonal B cell Activation and Antigen Specific Stimulation in Mice with Chronic Graft-Versus Host Reaction." manuscript. (1992)

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      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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