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人T细胞亚群中的外切5'-核苷酸酶活性。低丙种球蛋白血症患者中OKT4+和OKT8+细胞中外切5'-核苷酸酶阳性细胞数量减少。

Ecto-5'-nucleotidase activity in human T cell subsets. Decreased numbers of ecto-5'-nucleotidase positive cells from both OKT4+ and OKT8+ cells in patients with hypogammaglobulinemia.

作者信息

Thompson L F, Saxon A, O'Connor R D, Fox R I

出版信息

J Clin Invest. 1983 Apr;71(4):892-9. doi: 10.1172/jci110843.

Abstract

T lymphocytes from control subjects were separated into subsets using monoclonal antibodies of the OKT series and complement lysis and analyzed for ecto-5'-nucleotidase activity both by quantitative radiochemical assay and a histochemical stain. T cells from 15 control subjects contained 54+/-4% OKT4(+) (helper/inducer) cells and 32+/-3% OKT8(+) (cytotoxic/suppressor) cells. Total T cell ecto-5'-nucleotidase activity was 10.9+/-2.1 nmol/h per 10(6) cells with 25+/-7% positive by histochemical stain. Ecto-5'-nucleotidase activity in OKT4-enriched populations was 5.43+/-1.8 nmol/h per 10(6) cells with 14+/-2% positive by histochemical stain; that in OKT8-enriched populations was 17.1+/-5.9 nmol/h per 10(6) cells with 35+/-8% positive by histochemical stain. Two of four patients with congenital agammaglobulinemia and four of seven patients with common variable immunodeficiency had decreased proportions of OKT4(+) T cells with corresponding increases in the proportions of OKT8(+) T cells (OKT4/OKT8 = 0.60 to 1.0 as compared with 1.7+/-0.2 for control subjects). All four patients with congenital agammaglobulinemia, and three of seven patients with common variable immunodeficiency also had low T cell ecto-5'-nucleotidase activity (<5.5 nmol/h per 10(6) cells). Ecto-5'-nucleotidase activity in OKT4- enriched populations isolated from four patients with low total T cell activity was 2.85+/-0.90 nmol/h per 10(6) cells with 10+/-4% positive by histochemical stain; that in OKT8-enriched populations was 6.82+/-1.7 nmol/h per 10(6) cells with 7.5+/-3% positive by histochemical stain. Thus, the number of ecto-5'-nucleotidase positive cells is decreased, especially in the OKT8(+) subpopulation, and the low total T cell ecto-5'-nucleotidase activity seen in these patients is due to fewer positive cells rather than to substantially less activity per cell. Our data indicate that ecto-5'-nucleotidase activity defines two subpopulations of T lymphocytes (ecto-5'-nucleotidase positive and negative), the proportions of which are markedly altered in many patients with hypogammaglobulinemia. In preliminary studies with seven patients, increased numbers of ecto-5'-nucleotidase negative T cells appeared to correlate with increased suppressor T cell activity toward in vitro immunoglobulin synthesis. Therefore, ecto-5'-nucleotidase may be a useful cell surface marker in the study of imbalances of regulatory T cell subsets in patients with antibody synthesis disorders.

摘要

使用OKT系列单克隆抗体和补体裂解将来自对照受试者的T淋巴细胞分离成亚群,并通过定量放射化学测定和组织化学染色分析其外切5'-核苷酸酶活性。15名对照受试者的T细胞含有54±4%的OKT4(+)(辅助/诱导)细胞和32±3%的OKT8(+)(细胞毒性/抑制)细胞。总T细胞外切5'-核苷酸酶活性为每10(6)个细胞10.9±2.1 nmol/h,组织化学染色阳性率为25±7%。OKT4富集群体中的外切5'-核苷酸酶活性为每10(6)个细胞5.43±1.8 nmol/h,组织化学染色阳性率为14±2%;OKT8富集群体中的外切5'-核苷酸酶活性为每10(6)个细胞17.1±5.9 nmol/h,组织化学染色阳性率为35±8%。4例先天性无丙种球蛋白血症患者中的2例和7例常见可变免疫缺陷患者中的4例,OKT4(+)T细胞比例降低,OKT8(+)T细胞比例相应增加(OKT4/OKT8 = 0.60至1.0,而对照受试者为1.7±0.2)。所有4例先天性无丙种球蛋白血症患者和7例常见可变免疫缺陷患者中的3例,T细胞外切5'-核苷酸酶活性也较低(<每10(6)个细胞5.5 nmol/h)。从4例总T细胞活性低的患者中分离出的OKT4富集群体中的外切5'-核苷酸酶活性为每10(6)个细胞2.85±0.90 nmol/h,组织化学染色阳性率为10±4%;OKT8富集群体中的外切5'-核苷酸酶活性为每10(6)个细胞6.82±1.7 nmol/h,组织化学染色阳性率为7.5±3%。因此,外切5'-核苷酸酶阳性细胞的数量减少,尤其是在OKT8(+)亚群中,这些患者中总T细胞外切5'-核苷酸酶活性低是由于阳性细胞较少,而不是每个细胞的活性显著降低。我们的数据表明,外切5'-核苷酸酶活性定义了T淋巴细胞的两个亚群(外切5'-核苷酸酶阳性和阴性),在许多低丙种球蛋白血症患者中,这两个亚群的比例明显改变。在对7例患者的初步研究中,外切5'-核苷酸酶阴性T细胞数量增加似乎与体外免疫球蛋白合成的抑制性T细胞活性增加相关。因此,外切5'-核苷酸酶可能是研究抗体合成障碍患者调节性T细胞亚群失衡的有用细胞表面标志物。

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