Aarvak T, Strand E, Teigland J, Miossec P, Natvig J B
Institute of Immunology, Laboratory of Rheumatology Research and the Center for Rheumatic Diseases, The National Hospital, Oslo, Norway.
Scand J Immunol. 2001 Jul-Aug;54(1-2):100-8. doi: 10.1046/j.1365-3083.2001.00957.x.
Th1 and Th2 cells as defined by their cytokine profile are associated with the expression of the chemokine receptors CCR5 and CCR3, respectively. In committed human memory Th1 cells the cytokine profile is irreversibly expressed. However, it is not known if the chemokine receptor phenotypes of Th1 and Th2 cells are permanently associated to the cytokine profile or if it can be changed. To analyze the possibility of inducing a switch in chemokine receptor phenotype on memory Th cells we used differentiated memory Th cells isolated from synovial tissue (ST) samples of patients with rheumatoid arthritis (RA). Freshly isolated T cells, T-cell lines and T-cell clones from these tissues were manipulated with Th1 (interleukin (IL)-12 + anti IL-4) or Th2 (IL-4 + anti IL-12) inducing conditions. The surface expression of CCR5 and CCR3 was analyzed by flowcytometry and interferon (IFN)-gamma and IL-4 production by ELISA. A Th1-inducing cytokine environment increased the expression of CCR5 in Th1 cells and induced the expression of CCR5 in Th2 cells as compared to culture condition with only IL-2. Induction of CCR5 expression on Th2 clones was associated with secretion of some IFN-gamma. Moreover, the Th2-associated chemokine receptor CCR3 could be expressed on both Th1-dominant cell lines, and clones of Th1 and Th0 type after culture conditions with IL-4. This expression of CCR3 was associated with a reduced IFN-gamma production, but no IL-4 production could be induced. The IL-4-treated Th1 clones had a reduced migratory capacity against chemokines produced by ST cells compared to nonmanipulated T-cell clones. In contrast, the same IL-12-treated Th1 clones showed an increased migratory potential. Induction of the Th2-associated marker CCR3 on memory Th1 cells demonstrates that a change in chemokine receptor phenotype related to the Th2 type can be induced on terminally differentiated Th1 cells, without a change in the cytokine profile.
根据细胞因子谱定义的Th1和Th2细胞分别与趋化因子受体CCR5和CCR3的表达相关。在定型的人类记忆性Th1细胞中，细胞因子谱是不可逆表达的。然而，尚不清楚Th1和Th2细胞的趋化因子受体表型是与细胞因子谱永久相关，还是可以改变。为了分析诱导记忆性Th细胞趋化因子受体表型转换的可能性，我们使用了从类风湿性关节炎（RA）患者滑膜组织（ST）样本中分离出的分化记忆性Th细胞。用Th1（白细胞介素（IL）-12 + 抗IL-4）或Th2（IL-4 + 抗IL-12）诱导条件处理从这些组织中新鲜分离的T细胞、T细胞系和T细胞克隆。通过流式细胞术分析CCR5和CCR3的表面表达，并通过酶联免疫吸附测定法分析干扰素（IFN）-γ和IL-4的产生。与仅含IL-2的培养条件相比，Th1诱导性细胞因子环境增加了Th1细胞中CCR5的表达，并诱导了Th2细胞中CCR5的表达。Th2克隆上CCR5表达的诱导与一些IFN-γ的分泌相关。此外，在含IL-4的培养条件后，Th2相关趋化因子受体CCR3可以在以Th1为主的细胞系以及Th1和Th0型克隆上表达。CCR3的这种表达与IFN-γ产生减少相关，但不能诱导IL-4产生。与未处理的T细胞克隆相比，经IL-4处理的Th1克隆对ST细胞产生的趋化因子的迁移能力降低。相反，相同的经IL-12处理的Th1克隆显示出增加的迁移潜力。在记忆性Th1细胞上诱导Th2相关标志物CCR3表明，在终末分化的Th1细胞上可以诱导与Th2型相关的趋化因子受体表型改变，而细胞因子谱无变化。
