ICAM- MELANOMA-CELLS ARE RELATIVELY RESISTANT TO CD3-MEDIATED T-CELL LYSIS
ICAM- MELANOMA-CELLS ARE RELATIVELY RESISTANT TO CD3-MEDIATED T-CELL LYSIS
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DOI：
10.1002/ijc.2910460325
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发表时间：
1990-09-15
影响因子：
6.4
通讯作者：
BOLHUIS, RLH
中科院分区：
文献类型：
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作者：
BRAAKMAN, E;GOEDEGEBUURE, PS;BOLHUIS, RLH
T细胞的主要活化途径是通过T细胞受体（TCR）/CD 3复合物，其在功能上与各种辅助分子相关。我们研究了淋巴细胞功能相关抗原1/细胞间粘附分子1（LFA-1/ICAM-1）相互作用对细胞毒性T淋巴细胞（CTL）介导的CD 3/TCR裂解的贡献。以ICAM-1-或ICAM-1+肿瘤细胞为靶细胞，用抗CD 3-或抗LFA-1的异源交联单克隆抗体（MAb）桥接CTL与靶细胞，同时激活CTL。ICAM-1-黑色素瘤衍生的细胞系IgR 39对两种TCR α介导的CD 3-介导的裂解具有相对抗性。β +和TCT γ。δ + CTL，当与ICAMP-1+细胞系比较时。肿瘤坏死因子（TNF）诱导IgR 39细胞膜上的ICAM-1使这些细胞对CD 3介导的裂解更敏感。抗-ICMA-1单克隆抗体抑制这种TNF增强的对溶解的敏感性，直接证明ICAM-1的诱导在TNF诱导的IgR 39细胞对溶解的敏感性增加中是关键的。与ICAM-1+细胞相比，CTL与ICAM-1-细胞形成较低效率的缀合物。通过添加含有异源交联单抗的抗LFA-1，增强了CTL对ICAM-1-肿瘤细胞的自发和CD 3诱导的缀合物形成以及CD 3介导的裂解，从而模拟了CTL与靶细胞之间的LFA-1/ICAM-1相互作用。可溶性抗CD 18单克隆抗体抑制CD 3介导的ICAM-1靶细胞的CTL裂解，而不影响其结合物的形成。在缀合物形成后加入的抗LFA-1 MAb仍然抑制ICAM-1+或-肿瘤细胞的溶解。总而言之，这些发现表明LFA-1/ICAM-1相互作用通过增强的CTL靶细胞结合和偶联后共刺激信号的传递来共同激活CD 3/TCR介导的CTL溶解。
The primary activation pathway of T cells is via the T-cell receptor (TCR)/CD3 complex, which is functionally interrelated with various accessory molecules. We examined the contribution of the lymphocyte-function-associated antigen-1/intercellular adhesion molecule 1 (LFA-1/ICAM-1) interaction to CD3/TCR-mediated lysis by cytotoxic T lymphocytes (CTL). We used ICAM-1-or+ tumor cell lines as target cells and anti-CD3- or anti-LFA-1 containing hetero-cross-linked monoclonal antibody (MAb) to bridge CTL and target cells and simultaneously to activate CTL. The ICAM-1- melanoma-derived cell line IgR39 was relatively resistant to CD3-mediated lysis by both TCR.alpha..beta.+ and TCT.gamma..delta.+ CTL, when compared with ICAMP-1+ cell lines. Induction of ICAM-1 on the membrane of IgR39 cells by tumor necrosis factor (TNF) rendered these cells more susceptibile to CD3-mediated lysis. Anti-ICMA-1 MAb inhibited this TNF-enhanced susceptibility to lysis, directly demonstrating that the induction of ICAM-1 was critical in the TNF-induced increase in susceptibility to lysis of IgR39 cells. CTL formed less efficient conjugates with the ICAM-1- cells as compared to ICAM-1+ cells. Both spontaneous and CD3-induced conjugate formation as well as CD3-mediated lysis of ICAM-1- tumor cells by CTL were enhanced by the addition of anti-LFA-1 containing hetero-cross-linked MAb, thereby mimicking the LFA-1/ICAM-1 interaction between CTL and target cells. Soluble anti-CD18 MAb inhibited CD3-mediated lysis of ICAM-1- target cells by CTL without affecting their conjugate formation. Anti-LFA-1 MAb added after conjugate formation still inhibited lysis of both ICAM-1+or- tumor cells. Taken together, these findings suggest that the LFA-1/ICAM-1 interaction co-activates CD3/TCR-mediated lysis by CTL through both an enhanced CTL-target cell binding and the delivery of post-conjugate costimulatory signals.