Starkebaum G, Martin P J, Singer J W, Lum L G, Price T H, Kadin M E, Raskind W H, Fialkow P J
Clin Immunol Immunopathol. 1983 Apr;27(1):110-23. doi: 10.1016/0090-1229(83)90060-0.
A 67-year-old man with stable chronic neutropenia, lymphocytosis, multiple auto-antibodies, and recurring infections was studied in order to characterize the abnormal lymphocytes and the mechanism of neutropenia. One-half of the circulating mononuclear leukocytes were large granular lymphocytes that did not rosette with sheep erythrocytes and did not have surface immunoglobulin or receptors for C3 or IgG Fc. Virtually all of the mononuclear leukocytes, however, reacted with three monoclonal antibodies specific for mature T lymphocytes--OKT3, 3A1, and 12.1--the latter with a bimodal pattern on FACS analysis. The nonadherent, non-E-rosetting lymphocytes consisted of a homogeneous population of T cells with a novel phenotype: 3A1+, OKT3+, OKT8+, Ia+, 12.1+, OKT4-, 9.6-, 10.2-, Fc gamma receptor-. The abnormal phenotype of these cells suggested that they may have developed clonally. In spite of their OKT8+ phenotype, these lymphocytes were functionally abnormal, since they did not suppress B-cell immunoglobulin production in vitro. A humoral immune mechanism of neutropenia was indicated by increased levels of neutrophil-reactive IgG and in vivo kinetic studies with autologous neutrophils demonstrating shortened intravascular survival. The granulocyte turnover was normal, however, suggesting a blunted marrow response to the neutropenia. Corroborating the kinetic data, in vitro cultures of the patient's blood and marrow cells showed reduced numbers of granulocytic progenitors (CFU-C). Neither blood lymphocytes nor serum from the patient suppressed growth of allogeneic CFU-C nor did removal of OKT8+ cells from the marrow increase CFU-C expression. Thus, the disorder in this patient is characterized by proliferation of abnormal OKT8+ lymphocytes with impaired suppressor function. Our findings suggest that the neutropenia was due to anti-neutrophil autoantibodies that may have resulted from abnormal T-cell immunoregulation.
对一名67岁患有稳定型慢性中性粒细胞减少症、淋巴细胞增多症、多种自身抗体及反复感染的男性进行了研究，以明确异常淋巴细胞的特征及中性粒细胞减少的机制。循环单核白细胞中有一半是大颗粒淋巴细胞，它们不与绵羊红细胞形成玫瑰花结，表面也没有免疫球蛋白或C3或IgG Fc受体。然而，几乎所有单核白细胞都与三种针对成熟T淋巴细胞的单克隆抗体——OKT3、3A1和12.1发生反应，后者在流式细胞术分析中呈双峰模式。非黏附、非E玫瑰花结形成的淋巴细胞由具有新表型的T细胞同质群体组成：3A1 +、OKT3 +、OKT8 +、Ia +、12.1 +、OKT4 -、9.6 -、10.2 -、Fcγ受体 -。这些细胞的异常表型提示它们可能是克隆性发育而来。尽管这些淋巴细胞具有OKT8 +表型，但功能异常，因为它们在体外不能抑制B细胞免疫球蛋白的产生。中性粒细胞反应性IgG水平升高以及对自体中性粒细胞进行的体内动力学研究表明血管内生存期缩短，提示存在中性粒细胞减少的体液免疫机制。然而，粒细胞更新正常，提示骨髓对中性粒细胞减少的反应减弱。与动力学数据相符的是，患者血液和骨髓细胞的体外培养显示粒细胞祖细胞（CFU - C）数量减少。患者的血液淋巴细胞和血清均未抑制同种异体CFU - C的生长，从骨髓中去除OKT8 +细胞也未增加CFU - C的表达。因此，该患者疾病的特征是具有抑制功能受损的异常OKT8 +淋巴细胞增殖。我们的研究结果提示，中性粒细胞减少是由抗中性粒细胞自身抗体引起的，而这可能是异常T细胞免疫调节的结果。
