Nanki T, Hayashida K, El-Gabalawy H S, Suson S, Shi K, Girschick H J, Yavuz S, Lipsky P E
Department of Internal Medicine and Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235, USA.
J Immunol. 2000 Dec 1;165(11):6590-8. doi: 10.4049/jimmunol.165.11.6590.
Rheumatoid arthritis (RA) is characterized by the accumulation of CD4(+) memory T cells in the inflamed synovium. To address the mechanism, we analyzed chemokine receptor expression and found that the frequency of CXC chemokine receptor (CXCR)4 expressing synovial tissue CD4(+) memory T cells was significantly elevated. CXCR4 expression could be enhanced by IL-15, whereas stromal cell-derived factor (SDF)-1, the ligand of CXCR4, was expressed in the RA synovium and could be increased by CD40 stimulation. SDF-1 stimulated migration of rheumatoid synovial T cells and also inhibited activation-induced apoptosis of T cells. These results indicate that SDF-1-CXCR4 interactions play important roles in CD4(+) memory T cell accumulation in the RA synovium, and emphasize the role of stromal cells in regulating rheumatoid inflammation.
类风湿性关节炎（RA）的特征是炎症滑膜中CD4(+)记忆T细胞的积聚。为了探究其机制，我们分析了趋化因子受体的表达，发现表达CXC趋化因子受体（CXCR）4的滑膜组织CD4(+)记忆T细胞的频率显著升高。IL-15可增强CXCR4的表达，而CXCR4的配体基质细胞衍生因子（SDF）-1在RA滑膜中表达，且可通过CD40刺激而增加。SDF-1刺激类风湿滑膜T细胞迁移，同时抑制T细胞激活诱导的凋亡。这些结果表明，SDF-1-CXCR4相互作用在RA滑膜中CD4(+)记忆T细胞聚集中起重要作用，并强调了基质细胞在调节类风湿炎症中的作用。
