小児重症筋無力症患者の末梢血TH1様細胞と臨床症状発現の関連

血中抗AChR抗体価が陰性または疑陽性であった小児MG患児末梢血からヘルパーT (CD 4+CD 8-)細胞クローンを確立した, MG患者末梢血からIL-2およびIFN-γmRNA発現TH1様細胞クローンは確立されたが, IL-4およびIL-5mRNA発現TH2様細胞クローンは認められなかった.健康児末梢血からはTH1様細胞あるいはTH2様細胞クローン共に確立されなかった,臨床症状の増悪あるいは再発の認められたMG患児において,血中抗AChR抗体価は陰性あるいは疑陽性であったが,末梢血から確立されたTH細胞クローン中TH1様細胞クローン数の増加が認められた. TH1様細胞の産生するリンホカイン...

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Published in日本臨床免疫学会会誌 Vol. 16; no. 4; pp. 272 - 279
Main Authors 青木, 継稔, 瀬川, 昌也, 野村, 芳子, 四宮, 範明
Format Journal Article
LanguageJapanese
Published 日本臨床免疫学会 1993
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ISSN0911-4300
1349-7413
DOI10.2177/jsci.16.272

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Abstract 血中抗AChR抗体価が陰性または疑陽性であった小児MG患児末梢血からヘルパーT (CD 4+CD 8-)細胞クローンを確立した, MG患者末梢血からIL-2およびIFN-γmRNA発現TH1様細胞クローンは確立されたが, IL-4およびIL-5mRNA発現TH2様細胞クローンは認められなかった.健康児末梢血からはTH1様細胞あるいはTH2様細胞クローン共に確立されなかった,臨床症状の増悪あるいは再発の認められたMG患児において,血中抗AChR抗体価は陰性あるいは疑陽性であったが,末梢血から確立されたTH細胞クローン中TH1様細胞クローン数の増加が認められた. TH1様細胞の産生するリンホカインは細胞性免疫反応の発現あるいは調節に関与することから,血中抗AChR抗体価の陰性のMG患児の再発あるいは増悪に細胞性免疫反応が関係することが推測される.
AbstractList 血中抗AChR抗体価が陰性または疑陽性であった小児MG患児末梢血からヘルパーT (CD 4+CD 8-)細胞クローンを確立した, MG患者末梢血からIL-2およびIFN-γmRNA発現TH1様細胞クローンは確立されたが, IL-4およびIL-5mRNA発現TH2様細胞クローンは認められなかった.健康児末梢血からはTH1様細胞あるいはTH2様細胞クローン共に確立されなかった,臨床症状の増悪あるいは再発の認められたMG患児において,血中抗AChR抗体価は陰性あるいは疑陽性であったが,末梢血から確立されたTH細胞クローン中TH1様細胞クローン数の増加が認められた. TH1様細胞の産生するリンホカインは細胞性免疫反応の発現あるいは調節に関与することから,血中抗AChR抗体価の陰性のMG患児の再発あるいは増悪に細胞性免疫反応が関係することが推測される.
Author 瀬川, 昌也
青木, 継稔
野村, 芳子
四宮, 範明
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References 22) Schwimmbeck, P. L., Dyrberg, T., Drachman, D. B. et al.: Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor α-subunit that has biologic activity and react immunochemically with helpes simplex virus. J. Clin. Invest., 84: 1174-1180, 1989.
1) Drachman, D. M.: Myasthenia gravis. N. Engl. J. Med., 298: 136-142, 1978.
11) McMaster, G. K., Carmichael, G. G.: Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc. Natl. Acad. Sci. USA, 74: 4835-4846, 1977.
4) Limburg, P. D., The, T. H., Hummel-Tappel, E. et al.: Anti-acetylcholine receptor antibodies in myasthenia gravis. Part I Relation to clinical parameters in 250 patients. J. Neuro. Sci., 58: 357-370, 1983.
2) Soliven, B. C., Lange, D. J., Penn, A. S. et al. Seronegative myasthenia gravis. Neurology, 38: 514-517, 1988.
10) Hfler, D. A., Duby, A. D., Lee, S. J. et al.: Oligoclonal T cells in the cerebrospinal fluid of patients with multiple sclerosis. J. Exp. Med., 167: 1313-1319, 1988.
18) Shinomiya, N., Yata, J., Sasazuki, T.: T-cell subsets regulating anti-acetylcholine-receptor antibody formation in myasthenia gravis and characterization of suppressor T cell factors involved. Clin. Immunol. Immunopathol., 38: 182-190, 1984.
6) Mosmann, T. R., Cherwinski, H., Bond, M. W. et al.: Two types of murine helper T cell clone. 1 definition according to profiles of lymphokine activities and secreted proteins. J. Immunol., 136: 2348-2357, 1986.
8) Umetu, D. T., Jabara, H. H., DeKunyff, R. H. et al.: Functional heterogeneity among human inducer T cell clones. J. Immunol., 140: 4211-4219, 1988.
5) Bottomly, K.: A functional dichrotomy in CD 4+T lymphocytes. Immunol. Today, 9: 268-274, 1988.
20) Robinson, D. S., Hamid, Q., Ying, S. et al.: Predominant TH 2-like bronchoalveolar Tlymphocyte population in atopic asthma. N. Engl. J. Med., 30: 298-304, 1992.
7) Street, N. E., Schumacher, J. H., Fong, T. A. et al: Heterogeneity of mouse helper T cells: evidence from bulk cultures and limiting dilution cloning for precusor of TH 1 and TH 2 cells. J. Immunol., 144: 1629-1639, 1990.
15) Palliard, X., deWaaMalefji, R., Yssel, H. et al.: Simultaneous production of IL-2, IL-4, and IFN-γ by activated human CD 4+ and CD 8+T cell clones. J. Immunol., 141: 849-855, 1988.
19) Daynes, R. A., Araneo, B. A., Dowell, T. A. et al.: Regulation of murine lymphokine production in vivo. III The lymphoid tissue microenviroment exerts regulatory influence over T cell function. J. Exp. Med., 171: 979-996, 1990.
17) Kim, J., Woods, A., Becker-Dunn, Bottomly, K.: Distinct functional phenotypes of cloned Ia-restricted helper T cells. J. Exp. Med., 162: 188-196, 1985.
23) Mokhtrarian, F., Pino, M., Ofosu-Appiah, W. et al.: Phenotypic and functional characterization of T cells from patients with myasth. enia gravis. J. Clin. Invest., 86: 2099-2108, 1990.
12) Vincent, A.: Immunology of acetylcholine receptor in relation to myasthenia gravis. Physiol. Rev., 60: 756-824, 1980.
16) Broad, S. A., Benjamin, D., Hafler, D. A.: Restricted T cell expression of IL-2/IFN-γ mRNA in human inflammatory disease. J. Immunol., 147: 810-815, 1981.
21) Stefansson, K., Dieperink, M. E., Richman, D. P. et al.: Shearing of antigenic determinants between the nicotinic acetylcholine receptor and proteins in Escherichia coli, Proteus vulgaris and Klebsiella pneumonia. Possible role in the pathogenesis of myasthenia gravis. N. Engl. J. Med., 312: 221-225, 1985.
14) Berrih, S., Evelyne, M., Gaud, C. et al.: Anti-AChR antibodies, thymic histology and T cell subsets in myasthenia gravis. Neurology, 34: 66-71, 1984.
3) Verma, P. K., Oger, J. J-F.: Seronegative generalized myasthenia gravis. J. Neurol., 42: 586-589, 1992.
13) Vincent, A., Newson-Davis, J., Newton, P. et al.: Acetylcholine receptor antibody and clinical responses to thymectomy in myasthenia gravis. Neurology, 206: 79-88, 1983.
9) 瀬川昌也:小児重症筋無力症-潜在性全身型-.内科, 31: 1222~1226, 1973.
References_xml – reference: 19) Daynes, R. A., Araneo, B. A., Dowell, T. A. et al.: Regulation of murine lymphokine production in vivo. III The lymphoid tissue microenviroment exerts regulatory influence over T cell function. J. Exp. Med., 171: 979-996, 1990.
– reference: 21) Stefansson, K., Dieperink, M. E., Richman, D. P. et al.: Shearing of antigenic determinants between the nicotinic acetylcholine receptor and proteins in Escherichia coli, Proteus vulgaris and Klebsiella pneumonia. Possible role in the pathogenesis of myasthenia gravis. N. Engl. J. Med., 312: 221-225, 1985.
– reference: 7) Street, N. E., Schumacher, J. H., Fong, T. A. et al: Heterogeneity of mouse helper T cells: evidence from bulk cultures and limiting dilution cloning for precusor of TH 1 and TH 2 cells. J. Immunol., 144: 1629-1639, 1990.
– reference: 8) Umetu, D. T., Jabara, H. H., DeKunyff, R. H. et al.: Functional heterogeneity among human inducer T cell clones. J. Immunol., 140: 4211-4219, 1988.
– reference: 9) 瀬川昌也:小児重症筋無力症-潜在性全身型-.内科, 31: 1222~1226, 1973.
– reference: 5) Bottomly, K.: A functional dichrotomy in CD 4+T lymphocytes. Immunol. Today, 9: 268-274, 1988.
– reference: 15) Palliard, X., deWaaMalefji, R., Yssel, H. et al.: Simultaneous production of IL-2, IL-4, and IFN-γ by activated human CD 4+ and CD 8+T cell clones. J. Immunol., 141: 849-855, 1988.
– reference: 1) Drachman, D. M.: Myasthenia gravis. N. Engl. J. Med., 298: 136-142, 1978.
– reference: 16) Broad, S. A., Benjamin, D., Hafler, D. A.: Restricted T cell expression of IL-2/IFN-γ mRNA in human inflammatory disease. J. Immunol., 147: 810-815, 1981.
– reference: 14) Berrih, S., Evelyne, M., Gaud, C. et al.: Anti-AChR antibodies, thymic histology and T cell subsets in myasthenia gravis. Neurology, 34: 66-71, 1984.
– reference: 23) Mokhtrarian, F., Pino, M., Ofosu-Appiah, W. et al.: Phenotypic and functional characterization of T cells from patients with myasth. enia gravis. J. Clin. Invest., 86: 2099-2108, 1990.
– reference: 3) Verma, P. K., Oger, J. J-F.: Seronegative generalized myasthenia gravis. J. Neurol., 42: 586-589, 1992.
– reference: 20) Robinson, D. S., Hamid, Q., Ying, S. et al.: Predominant TH 2-like bronchoalveolar Tlymphocyte population in atopic asthma. N. Engl. J. Med., 30: 298-304, 1992.
– reference: 4) Limburg, P. D., The, T. H., Hummel-Tappel, E. et al.: Anti-acetylcholine receptor antibodies in myasthenia gravis. Part I Relation to clinical parameters in 250 patients. J. Neuro. Sci., 58: 357-370, 1983.
– reference: 2) Soliven, B. C., Lange, D. J., Penn, A. S. et al. Seronegative myasthenia gravis. Neurology, 38: 514-517, 1988.
– reference: 13) Vincent, A., Newson-Davis, J., Newton, P. et al.: Acetylcholine receptor antibody and clinical responses to thymectomy in myasthenia gravis. Neurology, 206: 79-88, 1983.
– reference: 22) Schwimmbeck, P. L., Dyrberg, T., Drachman, D. B. et al.: Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor α-subunit that has biologic activity and react immunochemically with helpes simplex virus. J. Clin. Invest., 84: 1174-1180, 1989.
– reference: 17) Kim, J., Woods, A., Becker-Dunn, Bottomly, K.: Distinct functional phenotypes of cloned Ia-restricted helper T cells. J. Exp. Med., 162: 188-196, 1985.
– reference: 10) Hfler, D. A., Duby, A. D., Lee, S. J. et al.: Oligoclonal T cells in the cerebrospinal fluid of patients with multiple sclerosis. J. Exp. Med., 167: 1313-1319, 1988.
– reference: 18) Shinomiya, N., Yata, J., Sasazuki, T.: T-cell subsets regulating anti-acetylcholine-receptor antibody formation in myasthenia gravis and characterization of suppressor T cell factors involved. Clin. Immunol. Immunopathol., 38: 182-190, 1984.
– reference: 6) Mosmann, T. R., Cherwinski, H., Bond, M. W. et al.: Two types of murine helper T cell clone. 1 definition according to profiles of lymphokine activities and secreted proteins. J. Immunol., 136: 2348-2357, 1986.
– reference: 11) McMaster, G. K., Carmichael, G. G.: Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc. Natl. Acad. Sci. USA, 74: 4835-4846, 1977.
– reference: 12) Vincent, A.: Immunology of acetylcholine receptor in relation to myasthenia gravis. Physiol. Rev., 60: 756-824, 1980.
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Title 小児重症筋無力症患者の末梢血TH1様細胞と臨床症状発現の関連
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