DIVERGENT T-CELL CYTOKINE PATTERNS IN INFLAMMATORY ARTHRITIS

DIVERGENT T-CELL CYTOKINE PATTERNS IN INFLAMMATORY ARTHRITIS
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DOI:
10.1073/pnas.91.18.8562
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发表时间:
1994-08-30
影响因子:
11.1
通讯作者:
SIEPER, J
SIEPER, J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SIMON, AK;SEIPELT, E;SIEPER, J

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炎性感染和变应性疾病中的主要免疫调节机制是控制辅助性T(Th)细胞的Th 1/Th 2亚群分泌的细胞因子的平衡。这在自身免疫性疾病中也可能是正确的;在细胞内细菌感染中阻止有效免疫应答的Th 2模式可能有利于自身免疫性疾病中的免疫抑制。比较了典型自身免疫性疾病(类风湿性关节炎)患者和具有相似滑膜病理但由持续外源性抗原驱动的疾病(反应性关节炎)患者滑膜组织中细胞因子表达的模式。我们筛选了12类风湿性关节炎和9反应性关节炎滑膜组织的PCR和原位杂交T细胞因子的表达。两种疾病之间的细胞因子模式显着不同;类风湿性关节炎样本表达的Th 1样模式,而在反应性关节炎干扰素γ的表达是伴随着白细胞介素4。通过原位杂交研究细胞因子的表达证实了通过PCR发现的结果;它们还显示了极低频率的精氨酸转录细胞。在双染色实验中,证实了白细胞介素4由CD 4细胞产生。这些实验有利于通过抑制性细胞因子对炎性风湿性疾病进行治疗干预的可能性。
A major immunoregulatory mechanism in inflammatory infections and allergic diseases is the control of the balance of cytokines secreted by Th1/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseases; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune diseases. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Th1-like pattern whereas in reactive arthritis interferon gamma expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confirmed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic diseases by means of inhibitory cytokines.