Nissinen Riikka, Leirisalo-Repo Marjatta, Tiittanen Minna, Julkunen Heikki, Hirvonen Hanna, Palosuo Timo, Vaarala Outi
Department of Molecular Medicine, National Public Health Institute, Biomedicum, PO Box 104, 00251 Helsinki, Finland.
J Rheumatol. 2003 Sep;30(9):1928-34.
To characterize cytokine and chemokine receptor profiles of T cells and monocytes in inflamed synovium and peripheral blood (PB) in patients with rheumatoid arthritis (RA) and other arthritides.
We studied PB and synovial fluid (SF) samples taken from 20 patients with RA and 9 patients with other arthritides. PB cells from 8 healthy adults were used as controls. CCR3, CCR5, and intracellular interferon-g (IFN-g) and interleukin 4 (IL-4) expression in CD8+ and CD8- T cell populations and in CD14+ cells were determined with flow cytometry.
Expression of CCR5 and CCR3 by CD8-, CD8+ T cells and CD14+ monocytes was increased in SF compared to PB cells in patients with RA and other arthritides. The number of CD8+ T cells spontaneously expressing IL-4 and IFN-g was higher in SF than in PB in RA patients. Spontaneous CCR5 expression was associated with intracellular IFN-g expression in CD8+ T cells derived from SF in RA. In CD8- T cells the ratio of CCR5+/CCR3+ cells was increased in patients with RA compared to patients with other arthritides. The number of PB CD8- T cells expressing IFN-g after mitogen stimulation was higher in controls than in patients. In PB monocytes the ratio of CCR5+/CCR3+ cells was increased in patients with RA compared to patients with other arthritides and controls.
T cells and monocytes infiltrating joints in RA and in other arthritides showed increased activation of both type 1 and type 2 immune markers. More pronounced type 1 immune response in joints, shown as an increased CCR5/CCR3 ratio, was found in the patients with RA versus those with other arthritides. Monocytes but not T cells in PB showed increased activation in RA.
描述类风湿关节炎(RA)和其他关节炎患者炎症滑膜及外周血(PB)中T细胞和单核细胞的细胞因子和趋化因子受体谱。
我们研究了20例RA患者和9例其他关节炎患者的PB和滑液(SF)样本。8名健康成年人的PB细胞用作对照。采用流式细胞术测定CD8⁺和CD8⁻ T细胞群体以及CD14⁺细胞中CCR3、CCR5、细胞内干扰素-γ(IFN-γ)和白细胞介素4(IL-4)的表达。
与RA和其他关节炎患者的PB细胞相比,SF中CD8⁻、CD8⁺ T细胞和CD14⁺单核细胞的CCR5和CCR3表达增加。RA患者SF中自发表达IL-4和IFN-γ的CD8⁺ T细胞数量高于PB。RA患者SF来源的CD8⁺ T细胞中,自发CCR5表达与细胞内IFN-γ表达相关。与其他关节炎患者相比,RA患者CD8⁻ T细胞中CCR5⁺/CCR3⁺细胞的比例增加。丝裂原刺激后,对照组PB中表达IFN-γ的CD8⁻ T细胞数量高于患者。与其他关节炎患者和对照组相比,RA患者PB单核细胞中CCR5⁺/CCR3⁺细胞的比例增加。
RA和其他关节炎患者关节中浸润的T细胞和单核细胞显示1型和2型免疫标志物的激活增加。与其他关节炎患者相比,RA患者关节中更明显的1型免疫反应表现为CCR5/CCR3比例增加。PB中的单核细胞而非T细胞在RA中显示激活增加。