Oh S K, Leung M F, Knee T, Williams J M
Department of Microbiology, Boston University School of Medicine, MA 02118.
Eur J Immunol. 1987 Oct;17(10):1403-9. doi: 10.1002/eji.1830171003.
A potent immunosuppressive factor isolated from malignant ascites fluids showed serological cross-reactivity with the E-receptor of human peripheral blood T lymphocytes. Thus, this factor was named suppressive E-receptor (SER) factor. In this study, we examined the effect of this immunosuppressor, SER, on lymphokine functions of human mononuclear cells participating in polyclonal T cell activation. SER is active at nanomolar concentrations in vitro and the inhibitory effect of SER was most pronounced when added at the initiation of stimulation with phytohemagglutinin or anti-T3 antibody. Concomitant with the inhibition on PHA-induced DNA synthesis, lymphocytes that were treated with SER failed to progress beyond G1 phase of cell cycle. These growth-arrested cells did expire after 7 days of culture in vitro. This anti-proliferative effect of SER was more easily demonstrated with normal lymphoid cells in culture than transformed cells or fibroblast cells. SER effectively interfered with the lympho-proliferative properties of interleukin 2 (IL 2) on human peripheral blood mononuclear cells and an IL 2-dependent murine cytotoxic T cell line. However, excess quantities of exogenous IL 2, especially when added in conjunction with IL 1, were able to partially overcome the ability of SER to inhibit T cell proliferation. In contrast to the inhibition on DNA synthesis of human lymphoblasts, expression of IL 2 receptor was only minimally inhibited by SER during the first 24 h of culture (24% inhibition at 12 h and 34% inhibition at 24 h) but it was followed by full expression of IL 2 receptor by 48 h. Thus, SER merely reduced the rate of expression of IL 2 receptor and was not able to inhibit the transcription of new message from activated T lymphocytes. Taken together, these studies indicate that SER acts as a noncytolytic anti-proliferative factor on immune responses that are mediated by T cells. SER appears to act on a relatively late event during T cell activation, perhaps on some portion of the DNA replication pathway.
从恶性腹水液中分离出的一种强效免疫抑制因子与人外周血T淋巴细胞的E受体呈现血清学交叉反应。因此，该因子被命名为抑制性E受体（SER）因子。在本研究中，我们检测了这种免疫抑制剂SER对参与多克隆T细胞激活的人单核细胞淋巴因子功能的影响。SER在体外纳摩尔浓度时具有活性，当在植物血凝素或抗T3抗体刺激开始时添加，SER的抑制作用最为明显。伴随着对PHA诱导的DNA合成的抑制，用SER处理的淋巴细胞无法进入细胞周期的G1期之后。这些生长停滞的细胞在体外培养7天后确实会死亡。SER的这种抗增殖作用在培养的正常淋巴细胞中比在转化细胞或成纤维细胞中更容易表现出来。SER有效干扰了白细胞介素2（IL 2）对人外周血单核细胞和IL 2依赖的小鼠细胞毒性T细胞系的淋巴细胞增殖特性。然而，过量的外源性IL 2，尤其是与IL 1联合添加时，能够部分克服SER抑制T细胞增殖的能力。与对人淋巴母细胞DNA合成的抑制相反，在培养的最初24小时内，SER对IL 2受体表达的抑制作用很小（12小时时抑制24%，24小时时抑制34%），但在48小时时IL 2受体完全表达。因此，SER只是降低了IL 2受体的表达速率，并且无法抑制活化T淋巴细胞新信息的转录。综上所述，这些研究表明SER作为一种非细胞溶解性抗增殖因子作用于由T细胞介导的免疫反应。SER似乎作用于T细胞激活过程中相对较晚的事件，可能作用于DNA复制途径的某些部分。
