Mechanisms of the anergy of T cells induced by varient types of soluble VCAM-1

1. 我们研究了可溶性VCAM-1如何影响TCR/CD3分子刺激诱导的Jurkat细胞的信号转导途径。1)在受刺激的Jurkat细胞中添加可溶性VCAM-1可抑制Ap-1、NF-AT和Oct-I与IL-2启动子区的结合，但对NF-kB的结合无抑制作用。2)可溶性VCAM-1诱导了受刺激Jurkat细胞钙调素依赖性激酶II的活性，但不影响局灶黏附分子的磷酸化。3)可溶性VCAM-1对T细胞的趋化作用依赖于rho、蛋白激酶C和钙调素依赖性激酶ii的活性。在此之前，我们报道了可溶性VCAM-1对T细胞功能的抑制作用。在本实验中，我们发现可溶性VCAM-1在T细胞的功能中发挥以下作用。1)与CD45RO^- T细胞相比，可溶性VCAM-1抑制CD45RO^+ T细胞的功能。2)可溶性VCAM-1诱导IL-2依赖性T细胞株、类风湿关节炎患者滑膜液T细胞和Jurkat细胞趋化。我们将可溶性VCAM-1的cDNA与IgGFc部分的cDNA连接，得到了可溶性VCAM-1的二聚体形式。

1. We examined how soluble VCAM-1 affects the pathway of signal transduction in Jurkat cells induced by the stimulation of TCR/CD3 molecules.1) Addition of soluble VCAM-1 to stimulated Jurkat cells inhibited the binding of Ap-1, NF-AT and Oct-I to the IL-2 promotor region but not that of NF-kB.2) Soluble VCAM-1 induced the activity of calmodulin dependent kinase II but not the phosphorylation of focal adhesion molecule in stimulated Jurkat cells.3) The chemotaxis of T cells by soluble VCAM-1 was dependent on the activity of rho, protein kinase C, and calmodulin dependent kinase II.2. Previously, we reported that soluble VCAM-1 acts inhibitory on the functions of T cells. In the present experiments, it was fount that soluble VCAM-1 play the following roles in the functions of T cells.1) Soluble VCAM-1 inhibited the function of CD45RO^+ T cells as compared that of CD45RO^- T cells.2) Soluble VCAM-1 induced the chemotaxis of IL-2 dependent T cell lines, synovial fluid T cells from rheumatoid arthritis patients and Jurkat cells.3. We developed a dimer form of soluble VCAM-1 by connecting cDNA of soluble VCAM-1 with cDNA of IgGFc portion.