Imbalanced expression of functional surface molecules in regulatory and effector T cells in systemic lupus erythematosus

Regulatory T (TREG) cells play an important role in maintaining immune tolerance and avoiding autoimmunity. We analyzed the expression of membrane molecules in TREG and effector T cells in systemic lupus erythematosus (SLE). TREG and effector T cells were analyzed for the expression of CTLA-4, PD1, CD28, CD95, GITR, HLA-DR, OX40, CD40L, and CD45RO in 26 patients with active disease, 31 with inactive disease, and 26 healthy controls. TREG cells were defined as CD25+/highCD127Ø/lowFoxP3+, and effector T cells were defined as CD25+CD127+FoxP3Ø. The ratio of TREG to effector T cells expressing GITR, PD1, HLA-DR, OX40, CD40L, and CD45RO was determined in the three groups. The frequency of TREG cells was similar in patients with SLE and controls. However, SLE patients had a decreased frequency of CTLA-4+TREG and CD28+TREG cells and an increased frequency of CD40L+TREG cells. There was a decrease in the TREG/effector-T ratio for GITR+, HLA-DR+, OX40+, and CD45RO+ cells, and an increased ratio of TREG/effector-T CD40L+ cells in patients with SLE. In addition, CD40L+TREG cell frequency correlated with the SLE disease activity index (P=0.0163). In conclusion, our findings showed several abnormalities in the expression of functionally critical surface molecules in TREG and effector T cells in SLE that may be relevant to the pathogenesis of this disease.

调节性T细胞（TREG）在维持免疫耐受、规避自身免疫方面发挥着关键作用。本研究分析了系统性红斑狼疮（SLE）患者体内TREG细胞与效应T细胞的膜分子表达情况。研究共纳入26例活动性SLE患者、31例非活动性SLE患者及26名健康对照者，对其中TREG细胞与效应T细胞的CTLA-4、PD1、CD28、CD95、GITR、HLA-DR、OX40、CD40L及CD45RO的表达水平进行了检测分析。
TREG细胞被定义为CD25阳性/高表达、CD127阴性/低表达且FoxP3阳性的细胞群，效应T细胞则被定义为CD25阳性、CD127阳性且FoxP3阴性的细胞群。本研究测定了三组人群中分别表达GITR、PD1、HLA-DR、OX40、CD40L及CD45RO的TREG细胞与效应T细胞的比值。
SLE患者与健康对照者的TREG细胞频率并无显著差异。但SLE患者体内CTLA-4+TREG细胞与CD28+TREG细胞的频率降低，而CD40L+TREG细胞的频率升高。在表达GITR+、HLA-DR+、OX40+及CD45RO+的细胞亚群中，TREG/效应T细胞比值出现下降；而SLE患者的TREG/效应T细胞CD40L+亚群比值则有所升高。此外，CD40L+TREG细胞频率与SLE疾病活动指数呈显著相关（P=0.0163）。
综上，本研究结果显示，SLE患者的TREG细胞与效应T细胞表面功能关键分子的表达存在多项异常，这些异常或与该病的发病机制相关。