Yamada Masato, Yagita Hideo, Inoue Hideko, Takanashi Tsuyoshi, Matsuda Hironori, Munechika Eiko, Kanamaru Yutaka, Shirato Isao, Tomino Yasuhiko, Matushima Kouji, Okumura Ko, Hashimoto Hiroshi
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Arthritis Rheum. 2002 Mar;46(3):735-40. doi: 10.1002/art.10112.
Some chemokine receptors, such as CCR5 and CCR4, are differentially expressed on Th1 and Th2 cells. To determine whether differential expression of the chemokine receptors occurs in patients with lupus nephritis, we examined the expression of CCR4 and CCR5 on peripheral blood lymphocytes and mononuclear cells infiltrated into the renal tissue of patients with lupus nephritis.
The expression of CCR4 and CCR5 on CD4+,CD45RO+ cells was analyzed by flow cytometry and compared between patients with systemic lupus erythematosus (SLE) and healthy controls. Correlation between the absolute number of CCR4+ or CCR5+ cells and clinical parameters was also analyzed. Mononuclear infiltrates in the renal tissue of SLE patients were analyzed for the expression of CCR4, CCR5, and CD4 by immunohistochemical staining.
The absolute number of CCR4+, but not CCR5+, T lymphocytes in the peripheral blood was significantly decreased in the patients with SLE compared with that in the healthy controls, and this positively correlated with the serum levels of C3 and CH50. Most of the CD4+ T lymphocytes that infiltrated into the renal tissue of the patients with lupus nephritis expressed CCR4, but not CCR5.
These results suggest that CCR4+ T lymphocytes in peripheral blood, which represent Th2 cells, preferentially migrate into the renal tissue of patients with lupus nephritis. The maldistribution of CCR4+ T lymphocytes might be involved in the pathogenesis of lupus nephritis.
一些趋化因子受体,如CCR5和CCR4,在Th1和Th2细胞上有差异表达。为了确定趋化因子受体的差异表达是否发生在狼疮性肾炎患者中,我们检测了狼疮性肾炎患者外周血淋巴细胞及浸润至肾组织的单核细胞上CCR4和CCR5的表达。
采用流式细胞术分析CCR4和CCR5在CD4+、CD45RO+细胞上的表达,并在系统性红斑狼疮(SLE)患者和健康对照者之间进行比较。还分析了CCR4+或CCR5+细胞绝对数与临床参数之间的相关性。通过免疫组化染色分析SLE患者肾组织中的单核细胞浸润情况,检测CCR4、CCR5和CD4的表达。
与健康对照者相比,SLE患者外周血中CCR4+ T淋巴细胞的绝对数显著降低,而CCR5+ T淋巴细胞绝对数无明显变化,且CCR4+ T淋巴细胞绝对数与血清C3和CH50水平呈正相关。浸润至狼疮性肾炎患者肾组织中的大多数CD4+ T淋巴细胞表达CCR4,而非CCR5。
这些结果表明,外周血中代表Th2细胞的CCR4+ T淋巴细胞优先迁移至狼疮性肾炎患者的肾组织。CCR4+ T淋巴细胞的分布异常可能参与了狼疮性肾炎的发病机制。