EVIDENCE FOR PROTEIN-TYROSINE KINASE INVOLVEMENT IN CD6-INDUCED T-CELL PROLIFERATION
EVIDENCE FOR PROTEIN-TYROSINE KINASE INVOLVEMENT IN CD6-INDUCED T-CELL PROLIFERATION
复制标题
DOI：
10.1006/cimm.1995.0006
复制
发表时间：
1995-11-01
影响因子：
4.3
通讯作者：
CHOW, SC
中科院分区：
文献类型：
--
作者：
OSORIO, LM;ORDONEZ, C;CHOW, SC
已有多项研究表明，在12-O-十四烷基佛波酯(TPA)处理的初始T细胞中加入可溶性抗CD6单抗可诱导细胞增殖。本研究表明，将抗CD6单抗固定或与兔抗鼠免疫球蛋白(RAM Ig)交联，可使TPA处理的T细胞的增殖倍数增加，用src家族蛋白酪氨酸激酶(PTK)抑制剂Herbimycin A有效地阻断抗CD6单抗IOR-T1诱导的T细胞增殖。在TPA存在下，将CD6受体与IOR-T1(随后是RAM Ig)交联后，对这些细胞中的细胞蛋白质进行分析，结果显示酪氨酸磷酸化水平增加。在IOR-T1/RAMIg、Ig和TPA刺激下，用0.5和1mU/mlHerbimycin A预处理18小时后，可完全抑制T细胞底物上酪氨酸的磷酸化。经IOR-T1/RAM、Ig和TPA处理后，相似浓度的去甲氧西林A也可抑制T细胞IL-2mRNA表达的增加和细胞增殖。此外，CD6受体与IOR-T1/RAMIg交联后，幼稚T细胞胞浆内游离钙离子浓度的升高也被去甲氧西林A所抑制。综上所述，我们的结果提示CD6介导的T细胞增殖是IL-2依赖的，并涉及严格依赖于蛋白激酶C激活的酪氨酸激酶活性。(C)1995年学术出版社。
Several studies have demonstrated that addition of soluble anti-CD6 mAbs to 12-O-tetradecanoyIphorbol 13-acetate (TPA)-treated naive T cells can induce cell proliferation, We showed in the present study that cell proliferation in TPA-treated T cell cultures can be enhanced several fold when the anti-CD6 mAbs are either immobilized or crosslinked with rabbit anti-mouse immunoglobulins (RAM Ig), Using a src family protein tyrosine kinase (PTK) inhibitor, herbimycin A, the cell proliferation induced by the anti-CD6 mAb, IOR-T1, in TPA-treated T cells were effectively abolished, Analysis of the cellular proteins in these cells after crosslinking the CD6 receptor with IOR-T1 (followed by RAM Ig) in the presence of TPA resulted in an increased level of tyrosine phosphorylation. Pretreatment of naive T cells with herbimycin A (0.5 and 1 mu g/ml) for 18 hr completely inhibited the tyrosine phosphorylation on cellular substrates in T cell cultures stimulated with IOR-T1/RAM Ig and TPA. Similar concentrations of herbimycin A also inhibited the increase in IL-2 mRNA expression and cell proliferation in T cell cultures after IOR-T1/RAM Ig and TPA treatment. Furthermore, the increase in cytosolic free Ca2(+) concentration in naive T cells after crosslinking of the CD6 receptor with IOR-T1/RAM Ig was also inhibited by herbimycin A. Taken together, our results suggest that CD6-mediated T cell proliferation is IL-2 dependent, and involves tyrosine kinase activity which is strictly dependent on protein kinase C activation. (C) 1995 Academic Press, Inc.