Peter H H, Friedrich W, Dopfer R, Müller W, Kortmann C, Pichler W J, Heinz F, Rieger C H
J Immunol. 1983 Nov;131(5):2332-9.
The immunologic work-up of eight infants with the clinical diagnosis of severe combined immunodeficiency (SCID) was performed with special emphasis on natural killer (NK) cell function and ontogeny. Contrary to previous reports, our study shows that not all SCID patients lack NK activity; some may even express very high NK- and antibody-dependent cellular cytotoxicity (ADCC). The present group of eight SCID infants was homogeneous with respect to normal levels of the purine metabolism enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP). They all had low serum Ig levels and were defective for specific antibody formation against BSA and diphtheria toxin (DiT). None of the infants' peripheral blood mononuclear cells (PBMC) proliferated significantly upon in vitro stimulation with PHA, concanavalin A (Con A), pokeweed mitogen (PWM), and irradiated allogeneic lymphocytes. Seven of eight patients, however, responded significantly to mitogenic factors present in a lectin-free interleukin 2 (IL 2) preparation, and two exhibited a positive costimulation as well with simultaneous exposure to IL 2 + Con A. The lymphocyte marker analysis revealed high percentages of OKT10+ cells in seven of eight infants, whereas peripheral T cells (OKT3+) with suppressor/killer (OKT8+) or helper/inducer (OKT4+) phenotypes were abnormally low in all infants with one exception. The PBMC of two patients formed low to normal percentages of E rosettes but expressed no B cell markers (B-/SCID). The six other infants had high percentages of B cells (B+/SCID) but lacked E rosette-forming cells. High NK and ADCC activity was found in the two B-/SCID patients. The B+/SCID infants either totally lacked NK and ADCC function (four of six) or expressed low to normal NK activity together with some T cell markers as revealed by monoclonal antibody staining but not by E rosette formation (two of six). From the data presented, an ontogenic model is proposed that assumes the status of an independent cell lineage in between T cells and monocytes for human NK cells, or that places these cells in close proximity to early differentiation steps of the T cell lineage. In any case, NK cell function clearly constitutes an additional parameter of heterogeneity in the immunologic analysis of SCID.
对八名临床诊断为严重联合免疫缺陷（SCID）的婴儿进行了免疫学检查，特别着重于自然杀伤（NK）细胞功能和个体发生。与先前的报告相反，我们的研究表明并非所有SCID患者都缺乏NK活性；有些患者甚至可能表现出非常高的NK细胞活性和抗体依赖性细胞毒性（ADCC）。目前这组八名SCID婴儿在嘌呤代谢酶腺苷脱氨酶（ADA）和嘌呤核苷磷酸化酶（PNP）的正常水平方面是同质的。他们的血清Ig水平均较低，并且针对牛血清白蛋白（BSA）和白喉毒素（DiT）的特异性抗体形成存在缺陷。在用PHA、刀豆蛋白A（Con A）、商陆有丝分裂原（PWM）和辐照的同种异体淋巴细胞进行体外刺激时，这些婴儿的外周血单个核细胞（PBMC）均未出现明显增殖。然而，八名患者中有七名对无凝集素白细胞介素2（IL 2）制剂中存在的促有丝分裂因子有明显反应，两名患者在同时暴露于IL 2 + Con A时也表现出阳性共刺激。淋巴细胞标志物分析显示，八名婴儿中有七名的OKT10 +细胞百分比很高，而除一名婴儿外，所有婴儿中具有抑制/杀伤（OKT8 +）或辅助/诱导（OKT4 +）表型的外周T细胞（OKT3 +）异常低。两名患者的PBMC形成E花环的百分比低至正常，但未表达B细胞标志物（B - /SCID）。其他六名婴儿的B细胞百分比很高（B + /SCID），但缺乏E花环形成细胞。在两名B - /SCID患者中发现了高NK和ADCC活性。B + /SCID婴儿要么完全缺乏NK和ADCC功能（六名中的四名），要么表现出低至正常的NK活性以及一些单克隆抗体染色显示但E花环形成未显示的T细胞标志物（六名中的两名）。根据所呈现的数据，提出了一种个体发生模型，该模型假定人类NK细胞在T细胞和单核细胞之间处于独立细胞谱系状态，或者将这些细胞置于靠近T细胞谱系早期分化步骤的位置。无论如何，NK细胞功能显然构成了SCID免疫学分析中异质性的一个额外参数。
