Ortaldo J R, Mason A T, O'Shea J J, Smyth M J, Falk L A, Kennedy I C, Longo D L, Ruscetti F W
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
J Immunol. 1991 Jun 1;146(11):3791-8.
CD3- large granular lymphocyte (LGL) express constitutive levels of functional IL-2R beta. TGF-beta inhibited several IL-2R beta-mediated events in LGL, including IL-2-induced NK and lymphokine-activating factor activities, IFN-gamma gene expression and secretion, and IL-2R alpha expression. TGF-beta inhibited these IL-2-induced LGL functions in a dose-dependent and reversible manner. By contrast, TGF-beta had little effect on LGL IL-2R beta expression and TGF-beta receptors were not induced by IL-2. Studies were performed to examine binding and internalization of radiolabeled IL-2. These experiments demonstrated that the rapid binding and internalization of [125I]IL-2 was not altered in CD3- LGL pretreated with TGF-beta. These internalization studies indicated that the TGF-beta inhibition represented postreceptor-binding events in NK cells. Further studies were initiated to examine signaling events in CD3- LGL. When IL-2-induced tyrosine phosphorylation events were examined, significant inhibition was seen of selected phosphoproteins in TGF-beta-pretreated cells. In addition, the ability of TGF-beta to also inhibit IL-2 induction of LGL IL-2R alpha and IFN-gamma mRNA expression was consistent with the hypothesis that posttranscriptional mechanisms were unlikely to be affected by TGF-beta. Collectively, these data indicated that TGF-beta inhibited IL-2-induced CD3- LGL functions and suggested that TGF-beta inhibition occurs either at the level of specific tyrosine phosphorylation and/or IL-2-induced transcriptional control factors.
CD3阴性大颗粒淋巴细胞（LGL）组成性表达功能性白细胞介素-2受体β（IL-2Rβ）。转化生长因子-β（TGF-β）抑制LGL中几种IL-2Rβ介导的事件，包括IL-2诱导的自然杀伤细胞和淋巴因子激活因子活性、干扰素-γ（IFN-γ）基因表达和分泌以及IL-2Rα表达。TGF-β以剂量依赖且可逆的方式抑制这些IL-2诱导的LGL功能。相比之下，TGF-β对LGL的IL-2Rβ表达影响很小，且IL-2不会诱导TGF-β受体。进行了研究以检测放射性标记的IL-2的结合和内化。这些实验表明，在用TGF-β预处理的CD3阴性LGL中，[125I]IL-2的快速结合和内化没有改变。这些内化研究表明，TGF-β的抑制作用代表了自然杀伤细胞中受体后结合事件。进一步开展研究以检测CD3阴性LGL中的信号转导事件。当检测IL-2诱导的酪氨酸磷酸化事件时，在TGF-β预处理的细胞中观察到选定磷蛋白受到显著抑制。此外，TGF-β抑制LGL的IL-2Rα和IFN-γ mRNA表达的能力也与转录后机制不太可能受TGF-β影响这一假设一致。总体而言，这些数据表明TGF-β抑制IL-2诱导的CD3阴性LGL功能，并提示TGF-β的抑制作用发生在特定酪氨酸磷酸化水平和/或IL-2诱导的转录控制因子水平。
