ナチュラルキラー細胞の機能異常
ナチュラルキラー (NK) 細胞が細胞障害活性のエフェクターとして働く場合には, まず標的細胞を認識して結合した後, 可溶性細胞障害因子 (NK soluble cytotoxic factors : NKCF) などの細胞破壊物質を放出してそれを破壊する.標的細胞を破壊するとそれから離れ, 他の標的細胞に向かって移動するリサイクリングを行う.したがって, NK細胞活性の低下は, (1) NK細胞数の減少, (2) 結合不全, (3) 破壊の障害, および (4) リサイクリングの障害で起こる.実際, そのような疾患が見いだされており, (1) 新生児, Chediak-Higashi症候群,...
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| Published in | 日本小児血液学会雑誌 Vol. 3; no. 1; pp. 2 - 8 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
特定非営利活動法人 日本小児血液・がん学会
1989
|
| Online Access | Get full text |
| ISSN | 0913-8706 1884-4723 |
| DOI | 10.11412/jjph1987.3.2 |
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| Abstract | ナチュラルキラー (NK) 細胞が細胞障害活性のエフェクターとして働く場合には, まず標的細胞を認識して結合した後, 可溶性細胞障害因子 (NK soluble cytotoxic factors : NKCF) などの細胞破壊物質を放出してそれを破壊する.標的細胞を破壊するとそれから離れ, 他の標的細胞に向かって移動するリサイクリングを行う.したがって, NK細胞活性の低下は, (1) NK細胞数の減少, (2) 結合不全, (3) 破壊の障害, および (4) リサイクリングの障害で起こる.実際, そのような疾患が見いだされており, (1) 新生児, Chediak-Higashi症候群, 重症複合型免疫不全症, 細網症 (hemophagocytic lymphohistiocytosis) では総NK細胞数または活性化NK細胞数が減少し, (2) 新生児とLFA-1 (lymphocyte function-associated antigen-1) /Mac-1 /P150, 95欠損症では標的細胞との結合不全があり, (3) 新生児, 白血病, myelodysplastic syndrome (MDS), エリテマトーデス, Chediak-Higashi 症候群, NKCF産生不全を伴う家族性NK細胞機能不全では破壊の障害が認められ, (4) 新生児, 白血病, Chediak-Higashi症候群, 先天性好中球減少症ではリサイクリングが低下している.NK細胞の機能不全の理解を容易にするため, われわれが経験した主な症例の臨床像と検査データの一部を提示した. |
|---|---|
| AbstractList | ナチュラルキラー (NK) 細胞が細胞障害活性のエフェクターとして働く場合には, まず標的細胞を認識して結合した後, 可溶性細胞障害因子 (NK soluble cytotoxic factors : NKCF) などの細胞破壊物質を放出してそれを破壊する.標的細胞を破壊するとそれから離れ, 他の標的細胞に向かって移動するリサイクリングを行う.したがって, NK細胞活性の低下は, (1) NK細胞数の減少, (2) 結合不全, (3) 破壊の障害, および (4) リサイクリングの障害で起こる.実際, そのような疾患が見いだされており, (1) 新生児, Chediak-Higashi症候群, 重症複合型免疫不全症, 細網症 (hemophagocytic lymphohistiocytosis) では総NK細胞数または活性化NK細胞数が減少し, (2) 新生児とLFA-1 (lymphocyte function-associated antigen-1) /Mac-1 /P150, 95欠損症では標的細胞との結合不全があり, (3) 新生児, 白血病, myelodysplastic syndrome (MDS), エリテマトーデス, Chediak-Higashi 症候群, NKCF産生不全を伴う家族性NK細胞機能不全では破壊の障害が認められ, (4) 新生児, 白血病, Chediak-Higashi症候群, 先天性好中球減少症ではリサイクリングが低下している.NK細胞の機能不全の理解を容易にするため, われわれが経験した主な症例の臨床像と検査データの一部を提示した. |
| Author | 小宮山, 淳 |
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| References | 7) Henkart PA, Millard PJ, Reynolds CW, et al : Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors. J Exp Med 160 : 75-93, 1984 28) Targan SR, Oseas R : The “lazy” NK cells of Chediak-Higashi syndrome. J Immunol 130 : 2671-2674, 1983 4) Wright SC, Bonavida B : Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity (CMC). I. Release of cytotoxic factors specific for NK-sensitive target cells (NKCF) during co-culture of NK effector cells with NK target cells. J Immunol 129 : 433-439, 1982 5) Farram E, Targan SR : Identification of human natural killer soluble cytotoxic factor (s) (NKCF) derived from NK-enriched lymphocyte populations : Specificity of generation and killing. J Immunol 130 : 1252-1256, 1983 19) Katz P, Zaytoun AM, Fauci AS : Deficiency of active natural killer cells in the Chediak-Higashi syndrome : Localization of the defect using a single cell cytotoxicity assay. J Clin Invest 69 : 1231-1238, 1982 29) Komiyama A, Kawai H, Yamada S, et al : A killing defect of natural killer cells with the absence of natural killer cytotoxic factors in a child with Hodgkin's disease. Blood 69 : 1686-1690, 1987 13) Timonen T, Ortaldo JR, Herberman RB : Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med 153 : 569-582, 1981 14) Abo T, Miller CA, Gartland GL, et al : Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life. J Exp Med 157 : 273-284, 1983 3) Ullberg M, Jondal M : Recycling and target binding capacity of human natural killer cells. J Exp Med 153 : 615-628, 1981 8) Schmidt RE, MacDermott RP, Bartley G, et al : Specific release of proteoglycans from human natural killer cells during target lysis. Nature 318 : 289-291, 1985 2) Grimm E, Bonavida B : Mechanism of cellmediated cytotoxicity at the single cell level. I. Estimation of cytotoxic T lymphocyte frequency and relative lytic deficiency. J Immunol 123 : 2861-2868, 1979 6) Degliantoni G, Murphy M, Kobayashi M, et al : Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor : Relationship with tumor necrosis factor and synergism with immune interferon. J Exp Med 162 : 1512-1530, 1985 16) Hercend TJ, Griffin JD, Bensussan A, et al : Generation of monoclonal antibodies to a human natural killer clone : Characterization of two natural killer-associated antigens, NKH la and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest 75 : 932-943, 1985 27) Katz P, Roder JC, Zaytoun AM, et al : Mechanisms of human cell-mediated cytotoxicity. II. Correction of the selective defect in natural killing in the Chediak-Higashi syndrome with inducers of intracellular cyclic GMP. J Immunol 129 : 297-302, 1982 22) Kawai H, Komiyama A, Aoyama K, et al : Absence of circulating natural killer (NK) cells in a child with erythrophagocytic lymphohistiocytosis lacking NK cell activity. Am J Hematol 28 : 107-112, 1988 26) Kobayashi K, Fujita K, Okino F, et al : An abnormality of neutrophil adhesion : Autosomal recessive inheritance associated with missing neutrophil glycoproteins. Pediatrics 73 : 606-610, 1984 10) Komiyama A, Yamazaki M, Yoda S, et al : Morphologic and functional heterogeneity of chronic neutropenia of childhood with normal neutrophil colony formation in vitro. Am J Hematol 11 : 175-182, 1981 12) Ammann A J, Hong R : Disorders of the T-cell system. Immunologic Disorders in Infants and Children, Stiehm ER, et al ed 2nd ed W. B. Saunders Philadelphia 1980,286-348 9) Shinkai Y, Takio K, Okumura K : Homology of perforin to the ninth component of complement (C9). Nature 334 : 525-527, 1988 1) Reynolds CW, Ortaldo JR : Natural killer activity : The definition of a function rather than a cell type. Immunol Today 8 : 172-174, 1987 30) Yabuhara A, Komiyama A, Kawai H, et al : Interleukin 2 improvement of impaired binding, killing and recycling of natural killer cells in neonates. Submitted for publication 23) Kohl S, Springer TA, Schmalsteg FC, et al : Defective natural killer cytotoxicity and polymorphonuclear leukocyte antibody-dependent cellular cytotoxicity in patients with LFA-1/ OKM-1 deficiency. J Immunol 133 : 2972-2978, 1984 24) Sanchez-Madrid F, Nagy J A, Robbins E, et al : A human leukocyte differentiation antigen family with distinct α-subunits and a commonβ-subunit : The lymphocyte function-associatedantigen (LFA-1), the C3bi complement receptor (OKM-1/Mac-1), and the p 150, 95 molecule. J Exp Med 158 : 1785-1803, 1983 18) Seki H, Ueno Y, Taga K, et al : Mode of in vitro augmentation of natural killer cell activity by recombinant human interleukin 2 : A comparative study of Leu-11+ and Leu-11-cell populations in cord blood and adult peripheral blood. J Immunol 135 : 2351-2356, 1985 20) Peter HH, Friedrich W, Dopfer R, et al : NK cell function in severe combined immunodeficiency (SCID) : Evidence of a common T and NK cell defect in some but not all SCID patients. J Immunol 131 : 2332-2339, 1983 15) Lanier LL, Le AM, Phillips JH, et al : Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol 131 : 1789-1796, 1983 21) Perez N, Virelizier J-L, Arenzana-Seisdedos F, et al : Impaired natural killer activity in lymphohistiocytosis syndrome. J Pediatr 104 : 569-573, 1984 25) Krensky AM, Mentzer S J, Clayberger C, et al : Heritable lymphocyte function-associated antigen-1 deficiency : Abnormalities of cytotoxicity and proliferation associated with abnormal expression of LFA-1. J Immunol 135 : 3102-3108, 1985 17) Phillips JH, Lanier LL : A model for the differentiation of human natural killer cells. Studies on the in vitro activation of Leu-11+ granular lymphocytes with a natural killersensitive tumor cell, K562. J Exp Med 161 : 1464-1482, 1985 11) Komiyama A, Kawai H, Yamada, et al : Impaired natural killer cell recycling in childhood chronic neutropenia with morphological abnormalities and defective chemotaxis of neutrophils. Blood 66 : 99-105, 1985 |
| References_xml | – reference: 10) Komiyama A, Yamazaki M, Yoda S, et al : Morphologic and functional heterogeneity of chronic neutropenia of childhood with normal neutrophil colony formation in vitro. Am J Hematol 11 : 175-182, 1981 – reference: 20) Peter HH, Friedrich W, Dopfer R, et al : NK cell function in severe combined immunodeficiency (SCID) : Evidence of a common T and NK cell defect in some but not all SCID patients. J Immunol 131 : 2332-2339, 1983 – reference: 17) Phillips JH, Lanier LL : A model for the differentiation of human natural killer cells. Studies on the in vitro activation of Leu-11+ granular lymphocytes with a natural killersensitive tumor cell, K562. J Exp Med 161 : 1464-1482, 1985 – reference: 18) Seki H, Ueno Y, Taga K, et al : Mode of in vitro augmentation of natural killer cell activity by recombinant human interleukin 2 : A comparative study of Leu-11+ and Leu-11-cell populations in cord blood and adult peripheral blood. J Immunol 135 : 2351-2356, 1985 – reference: 29) Komiyama A, Kawai H, Yamada S, et al : A killing defect of natural killer cells with the absence of natural killer cytotoxic factors in a child with Hodgkin's disease. Blood 69 : 1686-1690, 1987 – reference: 25) Krensky AM, Mentzer S J, Clayberger C, et al : Heritable lymphocyte function-associated antigen-1 deficiency : Abnormalities of cytotoxicity and proliferation associated with abnormal expression of LFA-1. J Immunol 135 : 3102-3108, 1985 – reference: 27) Katz P, Roder JC, Zaytoun AM, et al : Mechanisms of human cell-mediated cytotoxicity. II. Correction of the selective defect in natural killing in the Chediak-Higashi syndrome with inducers of intracellular cyclic GMP. J Immunol 129 : 297-302, 1982 – reference: 13) Timonen T, Ortaldo JR, Herberman RB : Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med 153 : 569-582, 1981 – reference: 15) Lanier LL, Le AM, Phillips JH, et al : Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol 131 : 1789-1796, 1983 – reference: 3) Ullberg M, Jondal M : Recycling and target binding capacity of human natural killer cells. J Exp Med 153 : 615-628, 1981 – reference: 16) Hercend TJ, Griffin JD, Bensussan A, et al : Generation of monoclonal antibodies to a human natural killer clone : Characterization of two natural killer-associated antigens, NKH la and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest 75 : 932-943, 1985 – reference: 7) Henkart PA, Millard PJ, Reynolds CW, et al : Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors. J Exp Med 160 : 75-93, 1984 – reference: 2) Grimm E, Bonavida B : Mechanism of cellmediated cytotoxicity at the single cell level. I. Estimation of cytotoxic T lymphocyte frequency and relative lytic deficiency. J Immunol 123 : 2861-2868, 1979 – reference: 8) Schmidt RE, MacDermott RP, Bartley G, et al : Specific release of proteoglycans from human natural killer cells during target lysis. Nature 318 : 289-291, 1985 – reference: 28) Targan SR, Oseas R : The “lazy” NK cells of Chediak-Higashi syndrome. J Immunol 130 : 2671-2674, 1983 – reference: 1) Reynolds CW, Ortaldo JR : Natural killer activity : The definition of a function rather than a cell type. Immunol Today 8 : 172-174, 1987 – reference: 21) Perez N, Virelizier J-L, Arenzana-Seisdedos F, et al : Impaired natural killer activity in lymphohistiocytosis syndrome. J Pediatr 104 : 569-573, 1984 – reference: 6) Degliantoni G, Murphy M, Kobayashi M, et al : Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor : Relationship with tumor necrosis factor and synergism with immune interferon. J Exp Med 162 : 1512-1530, 1985 – reference: 19) Katz P, Zaytoun AM, Fauci AS : Deficiency of active natural killer cells in the Chediak-Higashi syndrome : Localization of the defect using a single cell cytotoxicity assay. J Clin Invest 69 : 1231-1238, 1982 – reference: 4) Wright SC, Bonavida B : Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity (CMC). I. Release of cytotoxic factors specific for NK-sensitive target cells (NKCF) during co-culture of NK effector cells with NK target cells. J Immunol 129 : 433-439, 1982 – reference: 12) Ammann A J, Hong R : Disorders of the T-cell system. Immunologic Disorders in Infants and Children, Stiehm ER, et al ed 2nd ed W. B. Saunders Philadelphia 1980,286-348 – reference: 30) Yabuhara A, Komiyama A, Kawai H, et al : Interleukin 2 improvement of impaired binding, killing and recycling of natural killer cells in neonates. Submitted for publication – reference: 5) Farram E, Targan SR : Identification of human natural killer soluble cytotoxic factor (s) (NKCF) derived from NK-enriched lymphocyte populations : Specificity of generation and killing. J Immunol 130 : 1252-1256, 1983 – reference: 26) Kobayashi K, Fujita K, Okino F, et al : An abnormality of neutrophil adhesion : Autosomal recessive inheritance associated with missing neutrophil glycoproteins. Pediatrics 73 : 606-610, 1984 – reference: 14) Abo T, Miller CA, Gartland GL, et al : Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life. J Exp Med 157 : 273-284, 1983 – reference: 22) Kawai H, Komiyama A, Aoyama K, et al : Absence of circulating natural killer (NK) cells in a child with erythrophagocytic lymphohistiocytosis lacking NK cell activity. Am J Hematol 28 : 107-112, 1988 – reference: 9) Shinkai Y, Takio K, Okumura K : Homology of perforin to the ninth component of complement (C9). Nature 334 : 525-527, 1988 – reference: 11) Komiyama A, Kawai H, Yamada, et al : Impaired natural killer cell recycling in childhood chronic neutropenia with morphological abnormalities and defective chemotaxis of neutrophils. Blood 66 : 99-105, 1985 – reference: 23) Kohl S, Springer TA, Schmalsteg FC, et al : Defective natural killer cytotoxicity and polymorphonuclear leukocyte antibody-dependent cellular cytotoxicity in patients with LFA-1/ OKM-1 deficiency. J Immunol 133 : 2972-2978, 1984 – reference: 24) Sanchez-Madrid F, Nagy J A, Robbins E, et al : A human leukocyte differentiation antigen family with distinct α-subunits and a commonβ-subunit : The lymphocyte function-associatedantigen (LFA-1), the C3bi complement receptor (OKM-1/Mac-1), and the p 150, 95 molecule. J Exp Med 158 : 1785-1803, 1983 |
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| Snippet | ナチュラルキラー (NK) 細胞が細胞障害活性のエフェクターとして働く場合には, まず標的細胞を認識して結合した後, 可溶性細胞障害因子 (NK soluble cytotoxic factors : NKCF) などの細胞破壊物質を放出してそれを破壊する.標的細胞を破壊するとそれから離れ,... |
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| Title | ナチュラルキラー細胞の機能異常 |
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