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单克隆抗-T3抗体诱导非特异性细胞毒性

Induction of nonspecific cytotoxicity by monoclonal anti-T3 antibodies.

作者信息

Leeuwenberg J F, Spits H, Tax W J, Capel P J

出版信息

J Immunol. 1985 Jun;134(6):3770-5.

PMID:2580895
Abstract

The effects of monoclonal anti-T3 antibodies on the effector phase of cytotoxic T lymphocytes (CTL) were studied with respect to antigen-specific and antigen-nonspecific lysis of different target cells. Anti-T3 antibodies inhibited the antigen-specific lysis by CTL generated in mixed lymphocyte cultures (MLC), but they concomitantly augmented the nonspecific killing of third-party cells such as the cell lines Daudi, Raji, and K562. This nonspecific cytotoxicity was induced by various anti-T3 antibodies, whereas antibodies reactive with other antigens expressed on the cytotoxic effector cells lacked any such activity. Anti-T3 antibodies induced nonspecific cytotoxicity only when activated T cells, obtained by primary MLC, by repeated restimulation, or after cloning, were used. The antibodies had no effect on unstimulated peripheral T lymphocytes or thymocytes. The inhibition of the antigen-specific lysis and the induction of nonspecific lysis by anti-T3 was dose dependent, and both effects occurred at the same concentration range of anti-T3. F(ab')2 fragments of anti-T3 inhibited the specific lysis but were not able to induce cytotoxic activity, indicating that this induction is an Fc-dependent process. When different target cells were tested, only Fc receptor-positive cells were susceptible for this nonspecific cytotoxicity. Thus, anti-T3 antibodies have a dual effect on effector CTL: they inhibit antigen-specific lysis and concomitantly induce nonspecific lysis in an Fc-dependent way.

摘要

针对不同靶细胞的抗原特异性和抗原非特异性裂解,研究了单克隆抗T3抗体对细胞毒性T淋巴细胞(CTL)效应阶段的影响。抗T3抗体抑制了混合淋巴细胞培养(MLC)中产生的CTL的抗原特异性裂解,但同时增强了对第三方细胞(如细胞系Daudi、Raji和K562)的非特异性杀伤。这种非特异性细胞毒性由多种抗T3抗体诱导,而与细胞毒性效应细胞上表达的其他抗原反应的抗体则缺乏任何此类活性。只有当使用通过初次MLC、反复再刺激或克隆获得的活化T细胞时,抗T3抗体才会诱导非特异性细胞毒性。这些抗体对未刺激的外周T淋巴细胞或胸腺细胞没有影响。抗T3对抗原特异性裂解的抑制和非特异性裂解的诱导呈剂量依赖性,且两种效应都发生在抗T3的相同浓度范围内。抗T3的F(ab')2片段抑制特异性裂解,但不能诱导细胞毒性活性,这表明这种诱导是一个依赖Fc的过程。当测试不同的靶细胞时,只有Fc受体阳性细胞对这种非特异性细胞毒性敏感。因此,抗T3抗体对效应CTL有双重作用:它们抑制抗原特异性裂解,并以依赖Fc的方式同时诱导非特异性裂解。

相似文献

1
Induction of nonspecific cytotoxicity by monoclonal anti-T3 antibodies.单克隆抗-T3抗体诱导非特异性细胞毒性
J Immunol. 1985 Jun;134(6):3770-5.
2
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3
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T3 monoclonal antibody activation of nonspecific cytolysis: a mechanism of CTL inhibition.T3单克隆抗体激活非特异性细胞溶解:一种CTL抑制机制。
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Susceptibility of cytotoxic T lymphocyte (CTL) clones to inhibition by anti-T3 and anti-T4 (but not anti-LFA-1) monoclonal antibodies varies with the "avidity" of CTL-target interaction.细胞毒性T淋巴细胞(CTL)克隆对抗T3和抗T4(而非抗LFA - 1)单克隆抗体抑制作用的敏感性随CTL与靶细胞相互作用的“亲和力”而变化。
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Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3.抗T3单克隆抗体可诱导抗原特异性细胞毒性T细胞和抗原特异性增殖性T细胞克隆产生溶细胞活性。
Eur J Immunol. 1985 Jan;15(1):88-91. doi: 10.1002/eji.1830150117.
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Anti-T3 antibody both activates and inhibits the cytotoxic activity of human T cell clones.抗T3抗体既能激活又能抑制人T细胞克隆的细胞毒性活性。
Behring Inst Mitt. 1985 Aug(77):30-8.
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Clonal analysis of the involvement of T11 molecules in antigen receptor-mediated T lymphocyte functions.T11分子参与抗原受体介导的T淋巴细胞功能的克隆分析。
Behring Inst Mitt. 1985 Aug(77):39-47.

引用本文的文献

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Clin Exp Immunol. 2002 Dec;130(3):424-30. doi: 10.1046/j.1365-2249.2002.02012.x.
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Human T lymphocytes expressing a defined T-cell antigen receptor family specifically kill the hybridoma that makes the anti-receptor monoclonal antibody.表达特定T细胞抗原受体家族的人T淋巴细胞可特异性杀伤产生抗受体单克隆抗体的杂交瘤细胞。
Immunology. 1986 Nov;59(3):383-7.
3
MHC nonrestricted cytotoxic T cell clones with selective specificity from patients with transitional cell carcinoma (TCC) of the urinary bladder.
来自膀胱移行细胞癌(TCC)患者的具有选择性特异性的MHC非限制性细胞毒性T细胞克隆。
Cancer Immunol Immunother. 1988;27(3):205-12. doi: 10.1007/BF00205441.
4
Universal bispecific antibody for targeting tumor cells for destruction by cytotoxic T cells.用于靶向肿瘤细胞以被细胞毒性T细胞破坏的通用双特异性抗体。
Proc Natl Acad Sci U S A. 1988 Oct;85(20):7719-23. doi: 10.1073/pnas.85.20.7719.
5
Activation of human peripheral blood mononuclear cells by anti-T3: killing of tumor target cells coated with anti-target-anti-T3 conjugates.抗T3激活人外周血单个核细胞:杀伤包被有抗靶标-抗T3偶联物的肿瘤靶细胞。
Proc Natl Acad Sci U S A. 1986 Jun;83(12):4479-83. doi: 10.1073/pnas.83.12.4479.
6
A rat antibody against a structure functionally related to the mouse T-cell receptor/T3 complex.一种针对与小鼠T细胞受体/T3复合物功能相关结构的大鼠抗体。
Immunogenetics. 1988;28(6):455-8. doi: 10.1007/BF00355379.
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Studies on cytotoxicity generated in human mixed lymphocyte culture. IV. Interleukin 2 alone or from mixed lymphocyte culture yields natural killer-like cytotoxic cells distinct from allospecific cytotoxic T lymphocytes.人类混合淋巴细胞培养中产生的细胞毒性研究。IV. 单独的白细胞介素2或混合淋巴细胞培养产生的白细胞介素2可产生不同于同种特异性细胞毒性T淋巴细胞的自然杀伤样细胞毒性细胞。
Cancer Immunol Immunother. 1988;27(3):255-60. doi: 10.1007/BF00205448.
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Monoclonal antibody to a triggering structure expressed on rat natural killer cells and adherent lymphokine-activated killer cells.针对大鼠自然杀伤细胞和黏附性淋巴因子激活的杀伤细胞上表达的触发结构的单克隆抗体。
J Exp Med. 1989 Apr 1;169(4):1373-89. doi: 10.1084/jem.169.4.1373.
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T-cell receptor-specific monoclonal antibodies against a V beta 11-positive mouse T-cell clone.针对Vβ11阳性小鼠T细胞克隆的T细胞受体特异性单克隆抗体。
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J Exp Med. 1985 Dec 1;162(6):2089-106. doi: 10.1084/jem.162.6.2089.