Center for Human Genomics, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Cell Immunol. 2011;271(1):110-7. doi: 10.1016/j.cellimm.2011.06.010. Epub 2011 Jul 18.
Regulatory T cells (T(regs)) are critical for maintenance of peripheral tolerance via suppression of T-cell responses, and absence of T(regs) results in autoimmunity. The role of aberrations in the T(reg) pool for the development of systemic lupus erythematosus (SLE, lupus) remains uncertain. T(reg)-mediated generation of adenosine, dependent on the ectonucleotidase CD39, is an important mechanism for suppression of T-cell responses. We tested whether decreases in numbers of T(regs), and specifically CD39-expressing T(regs), are associated with human lupus. We studied 15 SLE patients, six patients with rheumatoid arthritis (RA) and 24 healthy controls. T(reg) phenotypic markers, including CD39 expression, were studied by flow cytometry. Varying numbers of sorted T(regs) cells were co-cultured with responder T (T(resp)) cells, with proliferation assessed by (3)H-thymidine incorporation. The proportion of T(regs) as defined by Foxp3(+) CD25(+high) CD127(-/low) was similar in lupus and control populations. CD39-expressing T(regs) comprised 37±13% of the T(reg) population in healthy controls and 36±21% in lupus subjects using nonsteroidal immunosuppressants to control active disease, but was nearly absent in five of six lupus subjects with minimally active disease. In contrast to healthy controls and lupus subjects without the CD39 defect, in SLE subjects with the CD39 defect, adenosine-dependent T(reg)-mediated suppression was nearly absent. These results suggest that functional defects in T(regs), rather than reduced T(reg) numbers, are important for the loss of peripheral tolerance in lupus. Presentation of this defect may serve as a biomarker for untreated disease.
调节性 T 细胞（Tregs）通过抑制 T 细胞应答来维持外周耐受至关重要，而 Tregs 的缺失会导致自身免疫。Treg 池中的异常在系统性红斑狼疮（SLE，狼疮）的发展中的作用仍不确定。依赖于外核苷酸酶 CD39 的 Treg 介导的腺苷生成是抑制 T 细胞应答的重要机制。我们测试了 Tregs 数量的减少，特别是 CD39 表达的 Tregs 的减少是否与人类狼疮有关。我们研究了 15 名狼疮患者、6 名类风湿关节炎（RA）患者和 24 名健康对照者。通过流式细胞术研究了 Treg 表型标志物，包括 CD39 表达。将分选的 Tregs 细胞与应答性 T（Tresp）细胞进行共培养，通过（3）H-胸腺嘧啶掺入评估增殖。Foxp3（+）CD25（+高）CD127（-/低）定义的 Tregs 比例在狼疮和对照组中相似。在使用非甾体类免疫抑制剂控制活动性疾病的狼疮患者和健康对照者中，CD39 表达的 Tregs 占 Treg 群体的 37±13%和 36±21%，但在活动性疾病较少的五名狼疮患者中几乎不存在。与健康对照者和无 CD39 缺陷的狼疮患者不同，在有 CD39 缺陷的 SLE 患者中，腺苷依赖性 Treg 介导的抑制几乎不存在。这些结果表明，Tregs 的功能缺陷而不是 Tregs 数量的减少对于狼疮中外周耐受的丧失很重要。该缺陷的表现可能作为未治疗疾病的生物标志物。
