Lotzová E, Savary C A, Champlin R E
Department of General Surgery, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
J Immunol. 1993 Jun 15;150(12):5263-9.
We have found that fully functional CD56+CD3- NK cells can be generated from highly enriched populations of CD34+ human bone marrow progenitors in long term bone marrow culture (LTBMC) with IL-2. Strong lytic activity against K-562 cells was observed after 2 to 3 weeks of culture and coincided with the appearance of CD56+CD3- large granular lymphocytes, which comprised 55 to 84% of cells. In contrast, lymphocytes generated from CD34- bone marrow cells were predominantly CD56-CD3+ T cells. The phenotypic profile of NK cells generated in LTBMC differed from that of IL-2-cultured peripheral blood NK cells. Specifically, a lower percentage of LTBMC-derived NK cells coexpressed CD16, CD2, CD7, and CD8 Ag. NK cells generated in LTMBC proliferated actively, with an expansion index ranging from two- to 200-fold. Furthermore, NK cells were generated from the CD34+CD33- hematopoietic subset, which had been depleted of the myeloid-committed progenitors (CD34+CD33+). Generation of cytotoxic NK cells in LTBMC was dependent on the dose of IL-2; although CD56+CD3- NK cells were generated in LTBMC supplemented with a broad range of doses (10 to 10(3) U/ml) of IL-2, the acquisition of full cytotoxic function required a high concentration of IL-2 (10(3) U/ml). These observations demonstrate the IL-2-driven differentiation of NK cells from early bone marrow progenitors and indicate that LTBMC may provide an excellent model for studies of NK cell lineage and differentiation in normal and pathologic conditions.
我们发现，在含有白细胞介素-2（IL-2）的长期骨髓培养（LTBMC）中，从高度富集的CD34+人骨髓祖细胞群体可生成功能完全的CD56+CD3-NK细胞。培养2至3周后观察到对K-562细胞有强烈的裂解活性，这与CD56+CD3-大颗粒淋巴细胞的出现相一致，这些细胞占细胞总数的55%至84%。相比之下，从CD34-骨髓细胞生成的淋巴细胞主要是CD56-CD3+T细胞。LTBMC中生成的NK细胞的表型特征与IL-2培养的外周血NK细胞不同。具体而言，LTBMC来源的NK细胞共表达CD16、CD2、CD7和CD8抗原的比例较低。LTMBC中生成的NK细胞积极增殖，扩增指数范围为2至200倍。此外，NK细胞是从CD34+CD33-造血亚群生成的，该亚群已去除了髓系定向祖细胞（CD34+CD33+）。LTBMC中细胞毒性NK细胞的生成依赖于IL-2的剂量；虽然在补充了广泛剂量（10至10(3)U/ml）IL-2的LTBMC中可生成CD56+CD3-NK细胞，但获得完全的细胞毒性功能需要高浓度的IL-2（10(3)U/ml）。这些观察结果证明了IL-2驱动早期骨髓祖细胞向NK细胞的分化，并表明LTBMC可能为研究正常和病理条件下NK细胞谱系及分化提供一个极好的模型。
