Wang X B, Zheng C Y, Giscombe R, Lefvert A K
Immunological Research Unit, Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Scand J Immunol. 2001 Nov;54(5):453-8. doi: 10.1046/j.1365-3083.2001.00985.x.
Cytotoxic T-lymphocyte-associated antigen (CTLA-4) is an important downregulator of T-cell activation. In order to analyze the expression and regulation of CTLA-4 on human peripheral T cells, CTLA-4 mRNA and protein expression were determined using analysis by reverse transcription-polymerase chain reaction (RT-PCR) and FACs, respectively. Intracellular CTLA-4 was constitutively expressed in unstimulated CD4+ and CD8+ T cells. Interleukin (IL)-2 induced a dose-dependent increase of both intracellular and surface expression of CTLA-4 (CD152). Most of the CD4+ and CD8+ cells expressing CTLA-4 also expressed CD25. Interferon (IFN)-gamma induced the upregulation of CTLA-4 expression via antigen-presenting cells (APC) activation. The CTLA-4delTM mRNA (550 bp) had a shorter half-life than the full length CTLA-4 mRNA and the expression was downregulated upon activation of the cells by treatment with IL-2. Given an inhibitory role of CTLA-4 and CD4+ CD25+ T cells in immune responses, the present findings suggest that IL-2-induced immunosuppression may result from its stimulatory effect of the CTLA-4 expression.
细胞毒性T淋巴细胞相关抗原(CTLA-4)是T细胞活化的重要负调节因子。为了分析CTLA-4在人外周血T细胞上的表达及调控情况,分别采用逆转录-聚合酶链反应(RT-PCR)分析和流式细胞术(FACs)测定CTLA-4 mRNA和蛋白表达。细胞内CTLA-4在未受刺激的CD4+和CD8+ T细胞中组成性表达。白细胞介素(IL)-2诱导CTLA-4(CD152)细胞内和表面表达呈剂量依赖性增加。大多数表达CTLA-4的CD4+和CD8+细胞也表达CD25。干扰素(IFN)-γ通过抗原呈递细胞(APC)活化诱导CTLA-4表达上调。CTLA-4delTM mRNA(550 bp)的半衰期比全长CTLA-4 mRNA短,在用IL-2处理激活细胞后其表达下调。鉴于CTLA-4和CD4+ CD25+ T细胞在免疫反应中的抑制作用,目前的研究结果表明,IL-2诱导的免疫抑制可能源于其对CTLA-4表达的刺激作用。