CD4+ PD-1+ T细胞作为独特的无反应性细胞在类风湿性关节炎滑液中积聚。

CD4+ PD-1+ T cells accumulate as unique anergic cells in rheumatoid arthritis synovial fluid.

作者信息

Hatachi Saori, Iwai Yoshiko, Kawano Seiji, Morinobu Sahoko, Kobayashi Masaya, Koshiba Masahiro, Saura Ryuichi, Kurosaka Masahiro, Honjo Tasuku, Kumagai Shunichi

机构信息

Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.

出版信息

J Rheumatol. 2003 Jul;30(7):1410-9.

PMID:12858435

Abstract

OBJECTIVE

The PD-1 receptor, whose deficiency in mice causes autoimmune diseases such as arthritis, is considered to be a negative regulator of activated T cells and to play a crucial role in peripheral tolerance. To clarify the involvement of the PD-1 system in rheumatoid arthritis (RA), we investigated PD-1 expression on synovial fluid (SF) T cells from patients with RA.

METHODS

FACS analysis for PD-1 was performed on SF T cells from 44 patients with RA and 6 with osteoarthritis (OA), and also on peripheral blood (PB) T cells from 12 RA patients and 7 healthy controls. Two-color analysis of cell surface PD-1 expression and the intracellular concentration of cytokine production was used to investigate CD4+ T cells from SF of patients with RA and PB from controls.

RESULTS

Scarcely any PD-1 expression was detected on control PB T or OA SF T cells. In contrast, PD-1+ cells made up 20.9 +/- 8.6% (mean +/- SD) of RA SF T cells. In RA SF, PD-1 was expressed more predominantly on CD4+ T cells than on CD8+ T cells. As well as expressing CD45RO and CXCR3, CD4+ PD-1+ T cells were mostly CTLA-4 positive and CD26 negative, and were enriched in CD45RB(low) cells. Intracellular cytokine staining revealed that CD4+ PD-1+, but not CD4+ PD-1-, T cells produced interleukin 10 (IL-10), and that CD4+ PD-1+ T cells produced less IL-2 than CD4+ PD-1- T cells.

CONCLUSION

PD-1+ T cells in RA SF are enriched, and phenotypic analysis suggests that these cells constitute a unique anergic T cell subset in RA SF.

摘要

目的

PD-1受体在小鼠体内缺乏会导致关节炎等自身免疫性疾病，被认为是活化T细胞的负调节因子，在外周免疫耐受中起关键作用。为阐明PD-1系统在类风湿关节炎（RA）中的作用，我们研究了RA患者滑液（SF）T细胞上PD-1的表达情况。

方法

对44例RA患者和6例骨关节炎（OA）患者的SF T细胞，以及12例RA患者和7例健康对照者的外周血（PB）T细胞进行PD-1的流式细胞术分析。采用细胞表面PD-1表达与细胞内细胞因子产生浓度的双色分析，研究RA患者SF中的CD4+ T细胞和对照者PB中的细胞。

结果

在对照PB T细胞或OA SF T细胞上几乎检测不到PD-1表达。相比之下，PD-1+细胞占RA SF T细胞的20.9±8.6%（平均值±标准差）。在RA SF中，PD-1在CD4+ T细胞上的表达比在CD8+ T细胞上更占优势。除了表达CD45RO和CXCR3外，CD4+ PD-1+ T细胞大多CTLA-4阳性、CD26阴性，且富含CD45RB(low)细胞。细胞内细胞因子染色显示，CD4+ PD-1+ T细胞而非CD4+ PD-1- T细胞产生白细胞介素10（IL-10），且CD4+ PD-1+ T细胞产生的IL-2比CD4+ PD-1- T细胞少。