Groux H, Sornasse T, Cottrez F, de Vries J E, Coffman R L, Roncarolo M G, Yssel H
Department of Human Immunology, DNAX Research Institute, Palo Alto, CA 94304, USA.
J Immunol. 1997 Jun 15;158(12):5627-31.
Differential expression of cytokine receptors accounts for an important regulatory mechanism in differentiation of Th1/Th2 subsets. Here, we report that human Th0 and Th2 clones constitutively express transcripts for the IFN-gammaR beta-chain, whereas mRNA for this signaling component of the IFN-gamma receptor is absent in Th1 clones. Activation of T cell clones, however, resulted in a transient induction or enhancement of IFN-gammaR beta-chain mRNA expression in Th1 clones and Th0/Th2 clones, respectively. IL-12-mediated Th1 cell differentiation of naive CD4+, CD45RA+ cord blood T cells, which constitutively express IFN-gammaR beta-chain mRNA, resulted in a loss of expression of this cytokine receptor chain after 6 to 12 days of culture. In contrast, Th2 populations, differentiated from CD4+, CD45RA+ cord blood T cells in the presence of IL-4, continued to express high levels of IFN-gammaR beta-chain transcripts. The loss of IFN-gammaR beta-chain expression in Th1 populations was accompanied by a failure of IFN-gamma to induce the expression of the IFN-gamma-inducible gene, IFN response factor-1, whereas IFN-gamma was effective in inducing IFN response factor-1 mRNA expression in Th0 and Th2 cells. These results indicate that down-regulation of the IFN-gammaR beta-chain correlates with impaired IFN-gamma-induced signaling in Th1 cells. Finally, Th2 populations, generated in the presence of both IL-4 and IFN-gamma, expressed levels of IFN-gammaR beta-chain transcripts similar to those produced by cells differentiated in the presence of IL-4 only, demonstrating that IFN-gamma does not modulate the expression of its receptor. Together, these data indicate that human Th0/Th2 and Th1 subsets, respectively, can be distinguished based on the expression of the IFN-gammaR beta-chain.
细胞因子受体的差异表达是Th1/Th2亚群分化中的一种重要调节机制。在此，我们报告人类Th0和Th2克隆组成性地表达IFN-γRβ链的转录本，而在Th1克隆中不存在这种IFN-γ受体信号成分的mRNA。然而，T细胞克隆的激活分别导致Th1克隆和Th0/Th2克隆中IFN-γRβ链mRNA表达的短暂诱导或增强。IL-12介导的初始CD4+、CD45RA+脐血T细胞向Th1细胞的分化，这些细胞组成性地表达IFN-γRβ链mRNA，在培养6至12天后导致该细胞因子受体链表达的丧失。相反，在IL-4存在下从CD4+、CD45RA+脐血T细胞分化而来的Th2群体继续高水平表达IFN-γRβ链转录本。Th1群体中IFN-γRβ链表达的丧失伴随着IFN-γ未能诱导IFN-γ诱导基因IFN反应因子-1的表达，而IFN-γ在诱导Th0和Th2细胞中IFN反应因子-1 mRNA表达方面是有效的。这些结果表明，IFN-γRβ链的下调与Th1细胞中IFN-γ诱导信号受损相关。最后，在IL-4和IFN-γ两者存在下产生的Th2群体表达的IFN-γRβ链转录本水平与仅在IL-4存在下分化的细胞产生的水平相似，表明IFN-γ不调节其受体的表达。总之，这些数据表明，人类Th0/Th2和Th1亚群可分别根据IFN-γRβ链的表达来区分。
