骨髄腫におけるLeu-7+細胞のサブセットの解析とNK細胞活性およびIg産生に及ぼす影響について
骨髄腫における液性免疫不全の発現機序を解明するために, Leu-7+細胞のサブセット, NK細胞活性およびB細胞のIg産生に及ぼす影響を骨髄腫26例と正常人20例について解析した. Leu-7+細胞のサブセットはtwo-color immunofluorescenceにより, NK細胞活性は末梢リンパ球をeffector, 51Cr標識K562細胞をtargetとして, B細胞のIg産生に及ぼす影響は末梢血より分取したLeu-7+細胞と正常単核球との混合培養により検討した.骨髄腫の末梢血Leu-7+細胞は33.4±11.0%で正常人の20.5±4.9%に比べ有意に増加し, Leu-7+ Leu...
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| Published in | 日本臨床免疫学会会誌 Vol. 9; no. 6; pp. 441 - 449 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本臨床免疫学会
1986
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| Online Access | Get full text |
| ISSN | 0911-4300 1349-7413 |
| DOI | 10.2177/jsci.9.441 |
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| Abstract | 骨髄腫における液性免疫不全の発現機序を解明するために, Leu-7+細胞のサブセット, NK細胞活性およびB細胞のIg産生に及ぼす影響を骨髄腫26例と正常人20例について解析した. Leu-7+細胞のサブセットはtwo-color immunofluorescenceにより, NK細胞活性は末梢リンパ球をeffector, 51Cr標識K562細胞をtargetとして, B細胞のIg産生に及ぼす影響は末梢血より分取したLeu-7+細胞と正常単核球との混合培養により検討した.骨髄腫の末梢血Leu-7+細胞は33.4±11.0%で正常人の20.5±4.9%に比べ有意に増加し, Leu-7+ Leu-2a+/Leu-7+比率(x)は52.6±13.1%で正常人29.5±12.3%に比べ約2倍に増加し,血中単クローン性Ig濃度(y)と相関(y=67.6x+286, r=0.55)を示した. NK細胞活性は骨髄腫48.6±22.9%,正常人53.1±15.0%で有意の差はなかった.混合培養の結果,骨髄腫のLeu-7+細胞は正常人のそれに比べIgG, IgA, IgMのすべての産生を強く抑制した.以上の成績から, T抗原(とくにLeu-2a)をco-expressしたLeu-7+細胞はNK細胞活性は低いが,骨髄腫におけるresidual Ig減少などの液性免疫不全に関与していることが明らかにされ,これらの細胞の増加は骨髄腫細胞によって誘導されている可能性が示唆された. |
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| AbstractList | 骨髄腫における液性免疫不全の発現機序を解明するために, Leu-7+細胞のサブセット, NK細胞活性およびB細胞のIg産生に及ぼす影響を骨髄腫26例と正常人20例について解析した. Leu-7+細胞のサブセットはtwo-color immunofluorescenceにより, NK細胞活性は末梢リンパ球をeffector, 51Cr標識K562細胞をtargetとして, B細胞のIg産生に及ぼす影響は末梢血より分取したLeu-7+細胞と正常単核球との混合培養により検討した.骨髄腫の末梢血Leu-7+細胞は33.4±11.0%で正常人の20.5±4.9%に比べ有意に増加し, Leu-7+ Leu-2a+/Leu-7+比率(x)は52.6±13.1%で正常人29.5±12.3%に比べ約2倍に増加し,血中単クローン性Ig濃度(y)と相関(y=67.6x+286, r=0.55)を示した. NK細胞活性は骨髄腫48.6±22.9%,正常人53.1±15.0%で有意の差はなかった.混合培養の結果,骨髄腫のLeu-7+細胞は正常人のそれに比べIgG, IgA, IgMのすべての産生を強く抑制した.以上の成績から, T抗原(とくにLeu-2a)をco-expressしたLeu-7+細胞はNK細胞活性は低いが,骨髄腫におけるresidual Ig減少などの液性免疫不全に関与していることが明らかにされ,これらの細胞の増加は骨髄腫細胞によって誘導されている可能性が示唆された. |
| Author | 小阪, 昌明 井石, 安比古 斉藤, 芳国 |
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| References | 7) Arai, S., Yamamoto, H., Itoh, K., et al.: Suppressive effect of human natural killer cells on pokeweed mitogen-induced B cell differentiation. J. Immunol., 131: 651-657, 1983. 19) Perri, R. T., Oken, M. M., Kay, N. E., et al.: Enhanced T cell suppression is directed toward sensitive circulating B cell in multiple myeloma. J. Lab. Clin. Med., 99: 512-519, 1982. 21) Maccario, R., Ugazio, A. G., Nespoli, L., et al.: Lymphocyte subpopulations in Down's syndrome: high percentage of circulating HNK-1+, Leu-2a+ cells. Clin. exp. Immunol., 57: 220-226, 1984. 24) Legendre, C. M., Guttmann, R. D., Hou, S. K., et al.: Two-color immunofluorescence and flow cytometry analysis of lymphocytes in long-term renal allotransplant recipients: Identification of a major Leu-7+/Leu-3+ subpopulation. J. Immunol., 135: 1061-1066, 1985. 1) 小阪昌明・岡川和人・井石安比古・他3名:骨髄腫患者の末梢血および骨髄におけるリンパ球サブセットの解析.医学のあゆみ, 131: 373～375, 1984. 4) Wang, C. Y., Good, R. A., Ammirati, P., et al.: Identification of a p69, 71 complex expressed on human T cells sharing determinants with B-type chronic lymphatic leukemic cells. J. Exp. Med., 151: 1539-1544, 1980. 13) Salmon, S. E.: Immunoglobulin synthesis and tumor kinetics of multiple myeloma. Semin. Hematol., 10: 135-147, 1973. 25) Maher, P., O'toole, C. M., Wreghitt, T. G., et al.: Cytomegalovirus infection in cardiac transplant recipients associated with chronic T cell subset ratio inversion with expansion of a Leu-7+ Ts-c+ subset. Clin. exp. Immunol., 62: 515-524, 1985. 8) Clement, L. T., Grossi, C. E., Gartland, G. L.: Morphologic and phenotypic features of the subpopulation of Leu-2+ cells that suppresses B cell differentiation. J. Immunol., 133: 2461-2468, 1984. 3) 斉藤和久・多田隈卓史:リンパ球の分離付着法.免疫実験操作法I: 93～94, 1971. 23) Landy, A., Poon, M. C., Abo, T., et al.: Immunologic studies in asymptomatic hemophilia patients. Relationship to acquired immune deficiency syndrome (AIDS). J. Clin. Invest., 71: 1500-1504, 1983. 17) Kennard, J., Zolla-Pazner, S.: Origin and function of suppressor macrophages in myeloma. J. Immunol., 124: 268-273, 1980. 20) Huwyler, T., Morell, A., Hirt, A., et al.: Correlation of natural killer cell function with Leu-7 reactivity in patients with humoral immunodeficiency. Clin. exp. Immunol., 56: 486-492, 1984. 5) Abo, T., Miller, C. A., Gartland, G. L., et al.: Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life. J. Exp. Med., 157: 273-284, 1983. 12) Abo, T., Cooper, M. D., Balch, C. M.: Characterization of HNK-1+ (Leu-7) human lymphocytes. I. Two distinct phenotypes of human NK cells with different cytotoxic capability. J. Immunol., 129: 1752-1757, 1982. 22) Velardi, A., Prchal, J. T., Prasthofer, E. F., et al.: Expression of NK-lineage markers on peripheral blood lymphocytes with T-helper (Leu-3+/T4+) phenotype in B cell chronic lymphocytic leukemia. Blood, 65: 149-155, 1985. 10) Banerjee, D., Thibert, R. F.: Natural killer-like cells found in B-cell compartments of human lymphoid tissues. Nature, 304: 270-272, 1983. 26) Pandolfi, F., Mandelli, F., Semenzato, G., et al.: Classification of patients with T-cell chronic lymphocytic leukemia and expantions of granular lymphocytes: Heterogeneity of Italian cases by a multiparameter analysis. J. Clin. Immunol., 4: 174-184, 1984. 9) Porwit-Ksiazek, A., Ksiazek, T., Biberfeld, P.: Leu-7+ (HNK-1+) cells. I. Selective compartmentalization of Leu-7+ cells with different immunophenotypes in lymphatic tissues and blood. Scand. J. Immunol., 18: 485-493, 1983. 16) Broder, S., Humphrey, R., Durm, M., et al.: Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma: Role of suppressor cells. N. Engl. J. Med., 293: 887-892, 1975. 6) Nabel, G., Allard, W. J., Cantor, H.: A cloned cell line mediating natural killer cell function inhibits immunoglobulin secretion. J. Exp. Med., 156: 658-663, 1982. 14) Heller, P., Bhoopalam, N., Cabana, V., et al.: The role of RNA in the immunological deficiency of plasmacytoma. Ann. N. Y. Acad. Sci., 207: 468-480, 1973. 18) Pezzutto, A., Semenzato, G., Agostini, C., et al.: Subpopulation of T-lymphocytes in multiple myeloma. Scand. J. Haematol., 26: 333-338, 1981. 2) 岡川和人・井口敬一・井石安比古・他1名:骨髄腫,マクログロブリン血症および良性M蛋白血症におけるT細胞サブセット:モノクローナル抗体による表面形質の検索とB細胞のIg産生能におよぼす効果の検討.日血会誌, 48: 1205～1213, 1985. 11) Pizzolo, G., Semenzato, G., Chilosi, M.: Distribution and heterogeneity of cells detected by HNK-1 monoclonal antibody in blood and tissues in normal, reactive and neoplastic conditions. Clin. exp. Immunol., 57: 195-206, 1984. 15) Lindsröm, F. D., Hardy, W. R., Eberle, B. J., et al.: Multiple myeloma and benign monoclonal gammopathy: Differentiation by immunofluorescence of lymphocytes. Ann. Intern. Med., 78: 837-844, 1973. |
| References_xml | – reference: 12) Abo, T., Cooper, M. D., Balch, C. M.: Characterization of HNK-1+ (Leu-7) human lymphocytes. I. Two distinct phenotypes of human NK cells with different cytotoxic capability. J. Immunol., 129: 1752-1757, 1982. – reference: 10) Banerjee, D., Thibert, R. F.: Natural killer-like cells found in B-cell compartments of human lymphoid tissues. Nature, 304: 270-272, 1983. – reference: 25) Maher, P., O'toole, C. M., Wreghitt, T. G., et al.: Cytomegalovirus infection in cardiac transplant recipients associated with chronic T cell subset ratio inversion with expansion of a Leu-7+ Ts-c+ subset. Clin. exp. Immunol., 62: 515-524, 1985. – reference: 18) Pezzutto, A., Semenzato, G., Agostini, C., et al.: Subpopulation of T-lymphocytes in multiple myeloma. Scand. J. Haematol., 26: 333-338, 1981. – reference: 24) Legendre, C. M., Guttmann, R. D., Hou, S. K., et al.: Two-color immunofluorescence and flow cytometry analysis of lymphocytes in long-term renal allotransplant recipients: Identification of a major Leu-7+/Leu-3+ subpopulation. J. Immunol., 135: 1061-1066, 1985. – reference: 17) Kennard, J., Zolla-Pazner, S.: Origin and function of suppressor macrophages in myeloma. J. Immunol., 124: 268-273, 1980. – reference: 21) Maccario, R., Ugazio, A. G., Nespoli, L., et al.: Lymphocyte subpopulations in Down's syndrome: high percentage of circulating HNK-1+, Leu-2a+ cells. Clin. exp. Immunol., 57: 220-226, 1984. – reference: 6) Nabel, G., Allard, W. J., Cantor, H.: A cloned cell line mediating natural killer cell function inhibits immunoglobulin secretion. J. Exp. Med., 156: 658-663, 1982. – reference: 13) Salmon, S. E.: Immunoglobulin synthesis and tumor kinetics of multiple myeloma. Semin. Hematol., 10: 135-147, 1973. – reference: 15) Lindsröm, F. D., Hardy, W. R., Eberle, B. J., et al.: Multiple myeloma and benign monoclonal gammopathy: Differentiation by immunofluorescence of lymphocytes. Ann. Intern. Med., 78: 837-844, 1973. – reference: 9) Porwit-Ksiazek, A., Ksiazek, T., Biberfeld, P.: Leu-7+ (HNK-1+) cells. I. Selective compartmentalization of Leu-7+ cells with different immunophenotypes in lymphatic tissues and blood. Scand. J. Immunol., 18: 485-493, 1983. – reference: 8) Clement, L. T., Grossi, C. E., Gartland, G. L.: Morphologic and phenotypic features of the subpopulation of Leu-2+ cells that suppresses B cell differentiation. J. Immunol., 133: 2461-2468, 1984. – reference: 22) Velardi, A., Prchal, J. T., Prasthofer, E. F., et al.: Expression of NK-lineage markers on peripheral blood lymphocytes with T-helper (Leu-3+/T4+) phenotype in B cell chronic lymphocytic leukemia. Blood, 65: 149-155, 1985. – reference: 20) Huwyler, T., Morell, A., Hirt, A., et al.: Correlation of natural killer cell function with Leu-7 reactivity in patients with humoral immunodeficiency. Clin. exp. Immunol., 56: 486-492, 1984. – reference: 11) Pizzolo, G., Semenzato, G., Chilosi, M.: Distribution and heterogeneity of cells detected by HNK-1 monoclonal antibody in blood and tissues in normal, reactive and neoplastic conditions. Clin. exp. Immunol., 57: 195-206, 1984. – reference: 4) Wang, C. Y., Good, R. A., Ammirati, P., et al.: Identification of a p69, 71 complex expressed on human T cells sharing determinants with B-type chronic lymphatic leukemic cells. J. Exp. Med., 151: 1539-1544, 1980. – reference: 26) Pandolfi, F., Mandelli, F., Semenzato, G., et al.: Classification of patients with T-cell chronic lymphocytic leukemia and expantions of granular lymphocytes: Heterogeneity of Italian cases by a multiparameter analysis. J. Clin. Immunol., 4: 174-184, 1984. – reference: 23) Landy, A., Poon, M. C., Abo, T., et al.: Immunologic studies in asymptomatic hemophilia patients. Relationship to acquired immune deficiency syndrome (AIDS). J. Clin. Invest., 71: 1500-1504, 1983. – reference: 2) 岡川和人・井口敬一・井石安比古・他1名:骨髄腫,マクログロブリン血症および良性M蛋白血症におけるT細胞サブセット:モノクローナル抗体による表面形質の検索とB細胞のIg産生能におよぼす効果の検討.日血会誌, 48: 1205～1213, 1985. – reference: 7) Arai, S., Yamamoto, H., Itoh, K., et al.: Suppressive effect of human natural killer cells on pokeweed mitogen-induced B cell differentiation. J. Immunol., 131: 651-657, 1983. – reference: 16) Broder, S., Humphrey, R., Durm, M., et al.: Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma: Role of suppressor cells. N. Engl. J. Med., 293: 887-892, 1975. – reference: 1) 小阪昌明・岡川和人・井石安比古・他3名:骨髄腫患者の末梢血および骨髄におけるリンパ球サブセットの解析.医学のあゆみ, 131: 373～375, 1984. – reference: 19) Perri, R. T., Oken, M. M., Kay, N. E., et al.: Enhanced T cell suppression is directed toward sensitive circulating B cell in multiple myeloma. J. Lab. Clin. Med., 99: 512-519, 1982. – reference: 3) 斉藤和久・多田隈卓史:リンパ球の分離付着法.免疫実験操作法I: 93～94, 1971. – reference: 14) Heller, P., Bhoopalam, N., Cabana, V., et al.: The role of RNA in the immunological deficiency of plasmacytoma. Ann. N. Y. Acad. Sci., 207: 468-480, 1973. – reference: 5) Abo, T., Miller, C. A., Gartland, G. L., et al.: Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life. J. Exp. Med., 157: 273-284, 1983. |
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| Title | 骨髄腫におけるLeu-7+細胞のサブセットの解析とNK細胞活性およびIg産生に及ぼす影響について |
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