Gerli R, Bistoni O, Russano A, Fiorucci S, Borgato L, Cesarotti M E F, Lunardi C
Department of Clinical and Experimental Medicine, Section of Internal Medicine and Oncologic Sciences, Rheumatology Unit, University of Perugia, Italy.
Clin Exp Immunol. 2002 Sep;129(3):549-55. doi: 10.1046/j.1365-2249.2002.01913.x.
T-cell cytokines play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). Their detection in the joint, however, is impaired by the complex network present in the synovium. Although many synovial T cells show signs of previous activation, only a few express interleukin (IL)-2 receptor, marker of recent activation. The aim of this study was to analyse the cytokine production by in vivo activated (IL-2R +) T cells from RA at different stages of the disease. For this purpose, T cells were isolated from peripheral blood and synovial fluid of four patients with active RA, two at the onset of the disease, one in the early phase during treatment, one in long-lasting chronic phase. One patient was studied at the onset of the disease and 52 months later. Cells were initially expanded with a low dose of IL-2, cloned and analysed for cytokine production. The results showed a strong predominance of T helper (Th) 1 clones in the blood and a slight prevalence of Th0 clones in the joint of all the four patients. Interferon-gamma and IL-2 production was higher in the long-lasting RA, whereas IL-4 synthesis was prevalent in early RA. Enrichment in IL-10-producing clones was present only in the joint of the untreated patients. The longitudinal study confirmed the differences in cytokine production between early and late phases of disease. These data confirm that RA is mainly a Th1-driven condition. However, in vivo activated synovial T cells produce also Th2-type anti-inflammatory cytokines, such as IL-4 and IL-10. The synthesis of both cytokines is a feature of the very early phase of RA, although the selective recruitment of IL-10-producing T cells is quickly lost.
T细胞细胞因子在类风湿性关节炎（RA）的发病机制和病情进展中起着关键作用。然而，滑膜中存在的复杂网络阻碍了在关节中对它们的检测。尽管许多滑膜T细胞显示出先前激活的迹象，但只有少数表达白细胞介素（IL）-2受体，即近期激活的标志物。本研究的目的是分析疾病不同阶段RA患者体内活化的（IL-2R +）T细胞产生的细胞因子。为此，从4例活动性RA患者的外周血和滑液中分离T细胞，其中2例处于疾病发作期，1例处于治疗早期，1例处于长期慢性期。对1例患者在疾病发作期及52个月后进行了研究。细胞最初用低剂量IL-2进行扩增、克隆并分析细胞因子产生情况。结果显示，所有4例患者血液中T辅助（Th）1克隆占主导，关节中Th0克隆略有优势。长期RA患者中干扰素-γ和IL-2的产生较高，而早期RA中IL-4的合成占优势。仅在未治疗患者的关节中存在产生IL-10克隆的富集。纵向研究证实了疾病早期和晚期细胞因子产生的差异。这些数据证实RA主要是一种由Th1驱动的病症。然而，体内活化的滑膜T细胞也产生Th2型抗炎细胞因子，如IL-4和IL-10。两种细胞因子的合成是RA极早期阶段的一个特征，尽管产生IL-10的T细胞的选择性募集很快消失。
