Choudhry M A, Sir O, Sayeed M M
Department of Surgery, Loyola University Chicago Medical Center, Maywood, Illinois 60153, USA.
Shock. 2001 Mar;15(3):193-9. doi: 10.1097/00024382-200115030-00006.
TGF-beta is known to inhibit many of the immune cell functions including T cell proliferation and IL-2 production. The mechanism of such TGF-beta-mediated inhibition of T cell functions is poorly understood. The present study examined the effects of TGF-beta on the activation of protein tyrosine kinases (PTK) P56lck, P59fyn, and Zap-70, and protein tyrosine phosphatases (PTP) SHP-1 and SHP-2. A balance between the actions of PTK and PTP is critical for appropriate T cell activation. These studies were carried out using nylon wool-purified splenic T cells from healthy Sprague-Dawley rats. Results from these studies showed that incubation of T cells with TGF-beta inhibited the activation of P56lck, P59fyn and Zap-70. The decrease in these three protein tyrosine kinases was accompanied by an increase in the activation of the protein tyrosine phosphatase SHP-1. There was no change in the phosphorylation of SHP-2 with and without pretreatment of T cells with TGF-beta. The decrease in P56lck, P59fyn kinase activity, and Zap-70 phosphorylation was prevented when T cells were stimulated with anti-CD3 in the presence of pervanadate, an inhibitor of PTP. These results suggested that TGF-beta-mediated inhibition of P56lck, P59fyn, and Zap-70 is likely due to an up-regulation of protein tyrosine phosphatases such as SHP-1.
已知转化生长因子β（TGF-β）可抑制多种免疫细胞功能，包括T细胞增殖和白细胞介素-2的产生。然而，对于TGF-β介导的T细胞功能抑制机制，人们了解甚少。本研究检测了TGF-β对蛋白酪氨酸激酶（PTK）P56lck、P59fyn和Zap-70以及蛋白酪氨酸磷酸酶（PTP）SHP-1和SHP-2激活的影响。PTK和PTP作用之间的平衡对于T细胞的适当激活至关重要。这些研究使用了从健康的斯普拉格-道利大鼠脾脏中通过尼龙毛纯化的T细胞进行。这些研究结果表明，用TGF-β孵育T细胞会抑制P56lck、P59fyn和Zap-70的激活。这三种蛋白酪氨酸激酶的减少伴随着蛋白酪氨酸磷酸酶SHP-1激活的增加。无论是否用TGF-β预处理T细胞，SHP-2的磷酸化均无变化。当在过钒酸盐（一种PTP抑制剂）存在的情况下用抗CD3刺激T细胞时，P56lck、P59fyn激酶活性和Zap-70磷酸化的降低被阻止。这些结果表明，TGF-β介导的对P56lck、P59fyn和Zap-70的抑制可能是由于蛋白酪氨酸磷酸酶如SHP-1的上调所致。
