SOLUBLE HTLV-I TAX1 PROTEIN STIMULATES PROLIFERATION OF HUMAN LYMPHOCYTES

人类T细胞嗜淋巴细胞病毒I型（HTLV-I）与两种 成人T细胞白血病（ATL）和热带痉挛性 轻瘫/HTLV-I相关脊髓病（TSP/HAM）。 淋巴细胞 ATL和TSP/HAM患者均显示异常增殖特性 在文化中。 纯化的可溶性Tax 1蛋白可被 刺激未感染植物血凝素处理的人的增殖 外周血淋巴细胞（PBL）。 Tax 1的活性为IL-2的40- 70 刺激PBL的增殖。 细胞外Tax 1可诱导淋巴细胞增殖 浓度低至25 pM。 诱导的增殖反应 细胞外Tax 1伴随着内源性Tax 1的激活， 人白细胞介素-2受体α链（IL-2 R α）表达 淋巴细胞 PBL中IL-2 R α表达的功能激活 使用125 I IL-2结合测定证明了用Tax 1处理的细胞的细胞毒性。 在 此外，ELISA测定表明，在小鼠中可溶性IL-2 R α IL-2和Tax 1处理的细胞的培养基比对照组高13倍以上。 对照处理的细胞的培养基。 IL-2 R α的过度表达是一种常见的 部分ATL和TSP/HAM患者的临床特征。 的能力 细胞外Tax 1蛋白激活IL-2 R α的表达， 感染和未感染的淋巴细胞可能有助于异常的 ATL和TSP/HAM淋巴细胞均观察到淋巴细胞增殖。

Human T-cell lymphotropic virus type I (HTLV-I) is associated with two human diseases, adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). Lymphocytes from both ATL and TSP/HAM patients display abnormal proliferation properties in culture. Purified, soluble Tax1 protein can be taken up by, and stimulate proliferation of, uninfected phyto-hemagglutinin-treated human peripheral blood lymphocytes (PBLs). Tax1 was 40-70% as active as IL-2 in stimulating proliferation of PBLs. Lymphocyte proliferation can be induced at extracellular Tax1 concentrations as low as 25 pM. The proliferative response induced by extracellular Tax1 is accompanied by an activation of endogenous interleukin-2 receptor alpha chain (IL-2Ralpha) expression in human lymphocytes. Functional activation of IL-2Ralpha expression in PBLs treated with Tax1 was demonstrated using a 125I IL-2 binding assay. In addition, an ELISA assay demonstrated that soluble IL-2Ralpha in the media of IL-2 and Tax1-treated cells was over 13-fold greater than in the media of control-treated cells. Overexpression of IL-2Ralpha is a common clinical feature of some ATL and TSP/HAM patients. The ability of extracellular Tax1 protein to activate expression of IL-2Ralpha in both infected and uninfected lymphocytes may contribute to the abnormal lymphocyte proliferation observed with both ATL and TSP/HAM lymphocytes.