Herrmann F, Griffin J D, Meuer S G, Meyer zum Büschenfelde K H
J Immunol. 1986 Mar 1;136(5):1629-34.
Circulating mononuclear cells from a patient developing severe aplastic anemia during the course of non-A, non-B hepatitis were found to be virtually entirely composed of in vivo activated suppressor T cells (Ia+T8+). These cells were used to establish a new permanent cell line, termed SMAA, by using phytohemagglutinin, Ebstein-Barr virus-transformed irradiated B cells, allogeneic irradiated peripheral blood mononuclear cells, and recombinant interleukin 2 to investigate the relationship of aplastic anemia-derived circulating T cells to bone marrow failure. SMAA cells, now in continuous culture for more than 9 mo, were shown to inhibit proliferation of purified myeloid progenitors and their differentiation into early and late appearing neutrophil and eosinophil colonies by 90%, whereas monocyte colonies were much less affected. Similarly, growth of erythroid colonies and bursts was almost completely inhibited, as was anti-mu-induced B cell proliferation and lectin-induced T cell proliferation. This inhibition of hematopoiesis was mediated by the release of a soluble factor that was sensitive to acid (pH 2), heat (56 degrees C), and trypsin. Monoclonal and polyclonal antibodies to interferon-gamma could abrogate the inhibitory effects of SMAA supernatant, but more than 10(4) neutralizing U/ml had to be added. The effects of SMAA could be duplicated by adding 10(4) U/ml of purified recombinant interferon-gamma to colony and proliferation assays. The concentration of interferon-gamma in SMAA supernatant was estimated to be greater than 3 X 10(3) National Institutes of Health reference U/ml by immunoradiometric assay. These results demonstrate that some patients with aplastic anemia have circulating T cells that are capable of prolonged in vitro secretion of interferon-gamma causing severe inhibition of in vitro hematopoiesis, and these cells can be expanded into permanent lines for studies on their regulatory properties.
在非甲非乙型肝炎病程中发生严重再生障碍性贫血的患者，其循环单核细胞实际上完全由体内活化的抑制性T细胞（Ia + T8 +）组成。利用植物血凝素、爱泼斯坦 - 巴尔病毒转化的经照射的B细胞、同种异体经照射的外周血单核细胞和重组白细胞介素2，使用这些细胞建立了一个新的永久细胞系，称为SMAA，以研究再生障碍性贫血来源的循环T细胞与骨髓衰竭之间的关系。现已连续培养超过9个月的SMAA细胞，显示可抑制纯化的髓系祖细胞的增殖及其向早期和晚期出现的中性粒细胞和嗜酸性粒细胞集落的分化达90%，而单核细胞集落受影响较小。同样，红系集落和爆式集落的生长几乎完全受到抑制，抗μ诱导的B细胞增殖和凝集素诱导的T细胞增殖也是如此。这种造血抑制是由一种对酸（pH 2）、热（56℃）和胰蛋白酶敏感的可溶性因子的释放介导的。针对干扰素 - γ的单克隆和多克隆抗体可消除SMAA上清液的抑制作用，但必须添加超过10⁴中和单位/毫升。通过向集落和增殖试验中添加10⁴单位/毫升的纯化重组干扰素 - γ，可重现SMAA的作用。通过免疫放射测定法估计，SMAA上清液中干扰素 - γ的浓度大于3×10³美国国立卫生研究院参考单位/毫升。这些结果表明，一些再生障碍性贫血患者具有循环T细胞，这些细胞能够在体外长时间分泌干扰素 - γ，导致体外造血受到严重抑制，并且这些细胞可以扩增为永久细胞系，用于研究其调节特性。
