INDUCTION OF CYTOTOXICITY IN RESTING HUMAN LYMPHOCYTES-T BOUND TO TUMOR-CELLS BY ANTIBODY HETEROCONJUGATES
INDUCTION OF CYTOTOXICITY IN RESTING HUMAN LYMPHOCYTES-T BOUND TO TUMOR-CELLS BY ANTIBODY HETEROCONJUGATES
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DOI：
10.1073/pnas.84.13.4611
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发表时间：
1987-07-01
影响因子：
11.1
通讯作者：
MULLEREBERHARD, HJ
中科院分区：
文献类型：
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作者：
JUNG, G;LEDBETTER, JA;MULLEREBERHARD, HJ
描述了外周人T细胞活化和由此产生的肿瘤细胞杀伤的体外模型。细胞毒性T淋巴细胞可以通过将人外周血单核细胞与抗CD 3单克隆抗体OKT 3孵育3天从静息淋巴细胞产生。外周血单核细胞中的细胞毒性也可以通过向培养基中加入抗靶OKT 3抗体缀合物和10%（体积/体积）胎牛血清来诱导。然而，当向培养基中加入20%（体积/体积）人血清时，T细胞的缀合物活化几乎完全被阻断。偶联物介导的外周血单核细胞活化通过向培养物中添加黑色素瘤靶细胞而在一定程度上恢复，并且通过含有抗靶细胞和抗CD 28抗体的第二偶联物而显著增强。单克隆抗体9.3（抗CD 28）与抗CD 3联合使用时，可提供T淋巴细胞活化的进展信号。因此，抗-CD 3和抗-CD 28的肿瘤靶细胞向静息人淋巴细胞的呈递导致T细胞活化，其不依赖于单核细胞，在人血清存在下进行，并导致肿瘤细胞杀伤。
An in vitro model for peripheral human T-cell activation and resultant tumor cell killing is described. Cytotoxic T lymphocytes may be generated from resting lymphocytes by incubation of human peripheral blood mononuclear cells for 3 days with the anti-CD3 monoclonal antibody OKT3. Cytotoxicity in peripheral blood mononclear cells can also be induced by adding an anti-target-OKT3 antibody conjugate and 10% (vol/vol) fetal calf serum to the culture medium. Conjugate activation of T cells was almost completely blocked, however, when 20% (vol/vol) human serum was added to the medium. Conjugate-mediated peripheral blood mononclear cells activation was restored to some extent by the addition of melanoma target cells to the culture and was markedly enhanced by a second conjugate containing anti-target cell and anti-CD28 antibody. Monoclonal antibody 9.3 (anti-CD28) provides a progression signal in T-lymphocyte activation when used in combination with anti-CD3. Thus, presentation by the tumor target cells of anti-CD3 and anti-CD28 to resting human lymphocytes causes T-cell activation, which is independent of monocytes, proceeds in the presence of human serum, and results in tumor cell killing.