Cohen S B, Katsikis P D, Chu C Q, Thomssen H, Webb L M, Maini R N, Londei M, Feldmann M
Kennedy Institute of Rheumatology, Sunley Division, London, UK.
Arthritis Rheum. 1995 Jul;38(7):946-52. doi: 10.1002/art.1780380710.
To characterize the cytokine profile of the activated T cell population derived from the synovial membrane of rheumatoid arthritis (RA) patients.
Interleukin-2 (IL-2) was used to select for in vivo-activated T cells from the synovial membrane of 2 patients with RA, and the cells were cloned nonspecifically. The cytokine production profile of these clones was compared with that of clones derived from peripheral blood monocytes (PBM) by stimulating all clones for 24 hours with immobilized anti-CD3 (coated at 10 micrograms/ml) or phorbol-12-myristate-13-acetate (10 ng/ml) plus soluble anti-CD3 (1 microgram/ml). Interferon-gamma (IFN gamma), IL-4, and IL-10, the cytokines that discriminate between Th1 and Th2 cells and are involved in immunoregulation, were assayed by enzyme-linked immunosorbent assay.
There was a difference in the cytokines produced by the clones derived from the rheumatoid membranes compared with clones derived from the periphery. Clones derived from both membranes and PBM were mostly IFN gamma-producers, i.e., either a Th0 or a Th1 profile. There was a high proportion of IFN gamma/high IL-10-producing cells derived from the joint, but not from the periphery. Of clones derived from the synovial membrane of each of 2 RA patients, 100% and 50% produced both 1-10 ng/ml IFN gamma and > 7 ng/ml IL-10, compared with < 7% of clones derived from normal or RA peripheral blood. In addition, when autologous membrane and PBM were compared, the mean concentration of IL-10 produced by the clones derived from the synovial membrane sample was significantly different from those produced by clones derived from peripheral blood (P < 0.02).
The cytokine profile of the T cell clones that were obtained from the RA joint after expansion with IL-2 is distinct from that of the T cells that are predominant in PBM. This supports the concept that the T cells subsets that accumulate in the joint are not a random sample. The high level of IL-10 production by clones derived from the synovium suggests that this cytokine may be a major contributor to the endogenous immunosuppression that occurs in RA.
对类风湿关节炎（RA）患者滑膜来源的活化T细胞群体的细胞因子谱进行特征分析。
用白细胞介素-2（IL-2）从2例RA患者的滑膜中筛选体内活化的T细胞，并对这些细胞进行非特异性克隆。通过用固定化抗CD3（以10微克/毫升包被）或佛波醇-12-肉豆蔻酸酯-13-乙酸酯（10纳克/毫升）加可溶性抗CD3（1微克/毫升）刺激所有克隆24小时，将这些克隆的细胞因子产生谱与外周血单核细胞（PBM）来源的克隆进行比较。采用酶联免疫吸附测定法检测干扰素-γ（IFNγ）、IL-4和IL-10，这些细胞因子可区分Th1和Th2细胞并参与免疫调节。
与外周来源的克隆相比，类风湿滑膜来源的克隆产生的细胞因子存在差异。来自滑膜和PBM的克隆大多产生IFNγ，即具有Th0或Th1细胞因子谱。关节来源的IFNγ/高IL-10产生细胞比例较高，而外周来源的比例较低。在2例RA患者滑膜来源的克隆中，100%和50%产生1 - 10纳克/毫升的IFNγ且IL-10>7纳克/毫升，相比之下，正常或RA外周血来源的克隆中这一比例<7%。此外，当比较自体滑膜和PBM时，滑膜样本来源的克隆产生的IL-10平均浓度与外周血来源的克隆产生的IL-10平均浓度有显著差异（P<0.02）。
用IL-2扩增后从RA关节获得的T细胞克隆的细胞因子谱与PBM中占优势的T细胞的细胞因子谱不同。这支持了关节中积累的T细胞亚群不是随机样本的概念。滑膜来源的克隆产生高水平的IL-10表明该细胞因子可能是RA中发生的内源性免疫抑制的主要促成因素。
