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LFA-1在胸腺细胞活化信号传导中的功能研究
FUNCTIONAL ROLES OF LFA-1 INVOLVED IN SIGNAL TRANSDUCTION FOR THYMOCYTE ACTIVATION
【摘要】 在ConA和固相抗CD3单抗刺激系统中,应用抗LFA-1/ICAM-1单抗,研究其在胸腺细胞活化中的功能作用,结果证明,培养初期加入可溶性抗LFA-1可完全阻断ConA活化胸腺细胞增殖,对固相抗CD3单抗诱导的胸腺细胞活化也表现出相同的抑制效应,但对ConA刺激24h后的胸腺细胞应答以及IL-1+IL-2诱导的胸腺细胞增殖无影响。在可溶性抗LFA-1单抗的存在下,ConA诱导胸腺细胞合成IL-2和IL-6的能力显著下降,IL-2R的表达降低。此外,当用固相抗LFA-1和固相抗CD3或用二抗交联LFA-1和CD3刺激胸腺细胞时,抗LFA-1则具有明显地促增殖应答效应,单纯固相抗LFA-1刺激或交联LFA-1均无诱导活化作用,研究结果表明,LFA-1是未成熟胸腺细胞活化的重要辅助分子之一,它可参与TCR/CD3途径介导的早期活化信号的传导,并为胸腺细胞表达IL-2R 和产生IL-2可能提供复合刺激信号。
【Abstract】 The biological significance of the signals triggered by the interaction of cell surface expressed LFA-1 and ICAM-1 has been investigated in Con A and immobilized anti-CD 3 mAb stimulated cultures. When added at the beginning of activation in the presence of Con A, soluble anti-LFA-1 and anti-ICAM-1 mAbs could strongly inhibit cell proliferation. Such inhibitory effect was also exhibited in the proli-ferative response of thymocytes to immobilized anti-CD 3 mAb activation. However, the soluble anti-LFA-1 mAb was unable to inhibit the proliferation of primed thymocytes preactivated with Con A for 24 h or of I L-1 + I L-2 activated fresh thymocytes. Anti-LFA-1 mAb could profoundlyinhibit Con A-induced thymocytes to produce IL-2 and IL-6 and to reduce IL-2 receptor expression. By contrast, anti-LFA-limmobilized on plastic plates together with immobilized anti-CD 3 mAbs or CD 3 cross-linking with LFA-1 by secondary antibodies resulted in an enhanced activa-ion signals for thymocytes to proliferate compared with that activated by anti-CD 3 alone. Thus, mAb to LFA-1 is a functional molecule for thymocyte activation, mediating signals contributed to very early phases of signal transduction through TCR/CD 3 pathway, and that LFA-1 might provide a costimulatory signal for expression of IL-2 R and IL-2 production.
【Key words】 Lymphocyte function-associated antigen-1. Intercellular adhesion molecule-1. Signal transduction. Thymocytes. TCR/CD3.;
- 【文献出处】 实验生物学报 ,Acta Biologiae Experimentalis Sinica , 编辑部邮箱 ,1994年04期
- 【分类号】R392;
- 【被引频次】1
- 【下载频次】31