Wang X J, Taga T, Yoshida K, Saito M, Kishimoto T, Kikutani H
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Blood. 1998 May 1;91(9):3308-14.
gp130 is a common signal-transducing receptor component for the interleukin-6 (IL-6) family of cytokines. To investigate the expression of gp130 in T-cell subsets and its regulation, anti-murine gp130 monoclonal antibody (MoAb) was used for flow cytometric analysis. In normal mice, gp130 was differentially expressed in thymocyte and splenic T-cell subpopulations defined by CD4/CD8 expression. In aged MRL/lpr mice, although gp130 expression was detectable in splenic CD4(+) or CD8(+) T cells, gp130 expression was significantly downregulated. Because serum levels of IL-6 and soluble IL-6 receptor (sIL-6R) are elevated in these mice, we examined the possibility that the downregulation of gp130 expression on splenic T cells might be produced in response to continuous activation of gp130 by high levels of serum IL-6. In transgenic mice overexpressing IL-6, gp130 expression in the splenic T cells was significantly decreased. After stimulation with IL-6 in vitro, the level of gp130 on CD4(+) or CD8(+) splenic T cells from normal mice was significantly decreased. These results suggest that the expression of gp130 in splenic T cells could be downregulated by the IL-6 stimulation under physiological or pathological circumstances.
gp130是细胞因子白细胞介素-6(IL-6)家族的一种常见信号转导受体成分。为了研究gp130在T细胞亚群中的表达及其调控,使用抗小鼠gp130单克隆抗体(MoAb)进行流式细胞术分析。在正常小鼠中,gp130在由CD4/CD8表达定义的胸腺细胞和脾T细胞亚群中差异表达。在老年MRL/lpr小鼠中,尽管在脾CD4(+)或CD8(+) T细胞中可检测到gp130表达,但gp130表达显著下调。由于这些小鼠血清中IL-6和可溶性IL-6受体(sIL-6R)水平升高,我们研究了脾T细胞上gp130表达下调可能是由于高水平血清IL-6持续激活gp130所致的可能性。在过表达IL-6的转基因小鼠中,脾T细胞中gp130表达显著降低。体外经IL-6刺激后,正常小鼠脾CD4(+)或CD8(+) T细胞上的gp130水平显著降低。这些结果表明,在生理或病理情况下,IL-6刺激可下调脾T细胞中gp130的表达。