Norii Mika, Yamamura Masahiro, Iwahashi Mitsuhiro, Ueno Akiko, Yamana Jiro, Makino Hirofumi
Department of Medicine and Clinical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Acta Med Okayama. 2006 Jun;60(3):149-57. doi: 10.18926/AMO/30745.
The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.
类风湿关节炎（RA）的炎症滑膜组织（ST）的特征是产生干扰素γ的Th1型CD4 + T细胞选择性积聚。在本研究中，我们调查了ST病变中Th1型CD4 +细胞的优势是否通过其通过Th1细胞相关趋化因子受体CXCR3和CCR5的选择性募集介导。RA的ST中的淋巴细胞聚集物包含大量CD4 + T细胞，这些细胞大多同时表达CXCR3和CCR5，但不表达CCR4。相比之下，与健康对照（HC）相比，RA患者血液中表达CXCR3和CCR5的CD4 +和CD8 + T细胞频率显著降低，尽管RA和HC之间表达CCR4的CD4 +和CD8 + T细胞频率没有差异。白细胞介素-15（IL-15）刺激后，血液CD4 + T细胞中的CXCR3、CCR5和CCR4表达以及CD8 + T细胞中的CXCR3表达增加。因此，RA中血液中Th1型CD4 + T细胞向ST的分布可能与趋化因子（CXCR3和CCR5配体）的局部表达有关，并且IL-15可能在增强CD4 + T细胞浸润上的这些趋化因子受体方面发挥作用。
