淋巴因子诱导的细胞毒细胞的体外诱导条件及其抗瘤作用

STUDY OF THE INDUCTION CONDITIONS OF LICC IN VITRO AND ITS ANTITUMOUR ACTIVITY

研究了细胞毒细胞(LICC)的体外诱导条件、体内外抗瘤作用及其前体细胞、效应细胞的特征。正常脾细胞(NS)与腹腔细胞(NPC)及消炎痛(INM)共育可产生LICC,最适条件为10%NPC加10^(-5)～10^(-7)mol/L INM。NPC中的Mφ通过释放细胞毒细胞分化因子(CCDF)诱导NS产生LICC活性,加入10^(-5)～10^(-7)mol/L INM可消除Mφ产生的前列腺素(PG)对LICC诱导的抑制作用。LICC的产生需IL-2和CCDF两种淋巴因子的协同作用,最适条件是10%～20%CCDF加0.3～1U/ml rIL-2。用直接和间接两种方法产生的LICC在体外具有同样的杀瘤作用。经冷靶抑制试验证实,LICC具有多克隆性质。LICC与S_(180)瘤细胞同时注入小鼠腹腔能明显延长荷瘤小鼠的存活期,表明LICC对荷瘤小鼠具保护作用。LICC的前体细胞为Thy-1^-,Lyt-2^-,效应细胞为Thy-1^+,Lyt-2^-。Lyt-1^+的Th对LICC的诱导起正向调节作用,而Lyt-2^+的Ts则起负向调节作用。

This paper studied the induction conditions of LICC in vitro, antitumour activities of LICC in vivo and vitro,characteristic of the effec- tors and precursors of LICC.LICC could be generated by culturing normal spleen cells with syngeneic peritoneal cells and indomethacin.The optimal condition was 10% peritoneal cells plus 10^(-5)—10^(-7)mol/L indomethacin.Mφ in peritoneal cells might induce the normal spleen cells to generate LICC activities by releasing CCDF.The addition of 10^(-5)—10^(-7)mol/L indomethacin could remove the restraint of PG produced by Mφ to LICC generation.It was established that CCDF produced by Mφ synergized with IL-2 to induce in vitro the generation of LICC in normal spleen cells.The optimal condi- tion was 10%—20% CCDF plus 0.3—1U/ml IL-2.Higher doses of IL-2 (3-9U/ml)reduced the LICC activities.It also demonstrated that cytotoxic spectrum was identical for the LICC generated by either the direct or indirect method.LICC could kill the tumour targets of different H-2 haplotypes,but didn′t kill lymphoblasts.Cold inhibition test showed the polyclonal nature of LICC.LICC could significantly increase the survival time of tumour-bearing mice when LICC and S_(180)cells were simultaneously inoculated into C57BL/6 mice,which showed that LICC had protective effect on tumour-bearing mice.The effectors of LICC were Thy-1^+, Lyt-2^-,and precursors wereThy-1^-,Lyt-2^-.During the induction of LICC,the Lyt-1^+ Th cells play a positive role and the Lyt-2^+ Ts cells play a negative role.