Silva M R, Ascensao J L
University of Nevada School of Medicine, Reno, Nevada 89520.
Br J Haematol. 1995 Jan;89(1):34-40. doi: 10.1111/j.1365-2141.1995.tb08914.x.
Human natural killer (NK) cells play an important role in first-line defence against primary and metastatic tumours. Their stimulation after autologous bone marrow transplantation (ABMT) may be useful to eradicate residual tumour cells. Human NK cells originate in bone marrow (BM) but little is known about their progenitors and lineage development. We studied NK cell ontogeny from BM progenitors obtained by 'purging' normal BM with 4-hydroperoxycyclophosphamide (4HC); this agent is known to destroy all but the most primitive BM progenitors. NK cells, defined by their phenotypic markers and cytolytic activity, could be generated from 4HC-treated BM cells during in vitro cultures over stromal BM feeder layers and in suspension cultures containing a mixture of soluble cytokines; Interleukine 2 appears to be essential for the full development of this population. A lag period exists before NK cells can be found in significant numbers in culture; this suggests that a delay in initiation of immunotherapy after ABMT ought to be considered, particularly when using purged marrow.
人类自然杀伤（NK）细胞在对原发性和转移性肿瘤的一线防御中发挥着重要作用。自体骨髓移植（ABMT）后对其进行刺激可能有助于根除残留的肿瘤细胞。人类NK细胞起源于骨髓（BM），但其祖细胞和谱系发育情况却知之甚少。我们研究了通过用4-氢过氧环磷酰胺（4HC）“净化”正常骨髓获得的骨髓祖细胞的NK细胞个体发生；已知该试剂能破坏除最原始的骨髓祖细胞外的所有细胞。通过其表型标志物和细胞溶解活性定义的NK细胞，可以在基质骨髓饲养层上的体外培养以及含有可溶性细胞因子混合物的悬浮培养中，由经4HC处理的骨髓细胞产生；白细胞介素2似乎对该群体的完全发育至关重要。在培养物中发现大量NK细胞之前存在一个延迟期；这表明在ABMT后应考虑延迟启动免疫治疗，特别是在使用净化骨髓时。
