Sugimura K, Ueda Y, Takeda K, Fukuda S, Tsukahara K, Habu Y, Fujiwara H, Azuma I
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Eur J Immunol. 1989 Aug;19(8):1357-64. doi: 10.1002/eji.1830190802.
The function of a human cytokine, lymphocyte blastogenesis inhibitory factor (LBIF), was characterized. To this end, LBIF was purified from crude supernatant of U-937 cells, a human macrophage-like cell line, by using fast protein liquid chromatography (FPLC). We demonstrated here that (a) the LBIF preparation completely inhibited phytohemagglutinin (PHA)-stimulated T cell proliferation; (b) however, in PHA-stimulated T lymphocytes LBIF inhibited neither interleukin (IL)2 production nor the expression of IL2 receptor (IL2R) light chain (CD25) which play a critical role for T cell proliferation; (c) LBIF arrested PHA-stimulated T lymphocytes at the G1 phase of cell cycle and inhibited entry into S phase, thus inhibiting lymphocyte proliferation. Wright-Giemsa's staining of the cells showed that PHA/LBIF-stimulated cells were arrested in early G1. In agreement with this result, LBIF strongly inhibited PHA-induced RNA synthesis. Further, LBIF inhibited the induction of the transferrin receptor which is normally expressed at the late G1 phase of the cell cycle. The inhibitory activity of LBIF was reversible. Thus, this study elucidated that LBIF arrests PHA-stimulated T lymphocytes at a point between the stages of IL2 production or IL2R light chain expression (in early G1) and transferrin receptor expression (in late G1). Taken together, these results suggest that there might be a control system of T cell proliferation distinct from the previously reported mechanisms, such as the inhibition of IL2 production or the inhibition of IL2R light chain (CD25) expression, and that LBIF might be an important molecule in the regulation of normal lymphocyte proliferation.
对一种人类细胞因子——淋巴细胞增殖抑制因子（LBIF）的功能进行了表征。为此，通过使用快速蛋白质液相色谱法（FPLC）从人巨噬细胞样细胞系U - 937细胞的粗提上清液中纯化出LBIF。我们在此证明：（a）LBIF制剂完全抑制了植物血凝素（PHA）刺激的T细胞增殖；（b）然而，在PHA刺激的T淋巴细胞中，LBIF既不抑制白细胞介素（IL）- 2的产生，也不抑制对T细胞增殖起关键作用的IL - 2受体（IL - 2R）轻链（CD25）的表达；（c）LBIF使PHA刺激的T淋巴细胞停滞在细胞周期的G1期，并抑制其进入S期，从而抑制淋巴细胞增殖。对细胞进行瑞氏 - 吉姆萨染色显示，PHA/LBIF刺激的细胞停滞在早期G1期。与该结果一致，LBIF强烈抑制PHA诱导的RNA合成。此外，LBIF抑制了转铁蛋白受体的诱导，该受体通常在细胞周期的G1晚期表达。LBIF的抑制活性是可逆的。因此，本研究阐明LBIF使PHA刺激的T淋巴细胞停滞在IL - 2产生或IL - 2R轻链表达阶段（早期G1期）与转铁蛋白受体表达阶段（晚期G1期）之间的某个点。综上所述，这些结果表明可能存在一个与先前报道的机制（如抑制IL - 2产生或抑制IL - 2R轻链（CD25）表达）不同的T细胞增殖控制系统，并且LBIF可能是正常淋巴细胞增殖调节中的一个重要分子。
