Toor A A, Lund T C, Miller J S
Department of Medicine, University of Minnesota Cancer Center, Harvard Street at East River Road, Minneapolis, MN 55455, USA.
Exp Hematol. 2001 Apr;29(4):499-506. doi: 10.1016/s0301-472x(00)00680-9.
Transcription factors are essential to govern differentiation along the lymphoid lineage from uncommitted hematopoietic stem cells. Although many of these transcription factors have putative roles based on murine knockout experiments, their function in human lymphoid development is less known and was studied further. Transcription factor expression in fresh and cultured adult human bone marrow and umbilical cord blood progenitors was evaluated. We found that fresh CD34(+)Lin(-) cells that are human leukocyte antigen (HLA)-DR(-) or CD38(-) constitutively express GATA-3 but not T-cell factor-1 (TCF-1) or Id-3. Culture with the murine fetal liver cell line AFT024 and defined cytokines was capable of inducing TCF-1 mRNA. However, no T-cell receptor gene rearrangement was identified in cultured progeny. Id-3, a basic helix loop helix factor with dominant negative function for T-cell differentiation transcription factors, also was upregulated and may explain unsuccessful T-cell maturation. To better understand the developmental link between natural killer (NK) cells derived from progenitors, we studied NK cell subsets circulating in blood. CD56(+bright), but not CD56(+dim), NK cells constitutively express TCF-1 by reverse transcriptase polymerase chain reaction and Western blot analysis. The TCF-1 isoform found in CD56(+bright) cells, which express lectin but not immunoglobulin class I recognizing inhibitory receptors, was identical to that induced in NK cell differentiation culture and was distinctly different from isoforms in T cells. These results suggest that TCF-1 does not target human killer immunoglobulin receptor genes, TCF-1 is uniquely expressed in circulating CD56(+bright) NK cells, and specific TCF-1 isoforms may play an important role in regulating NK differentiation from a common NK/T-cell progenitor.
转录因子对于调控未定向造血干细胞沿淋巴谱系的分化至关重要。尽管基于小鼠基因敲除实验，许多此类转录因子具有推定作用，但其在人类淋巴发育中的功能鲜为人知，因此进行了进一步研究。评估了新鲜和培养的成人骨髓及脐带血祖细胞中转录因子的表达。我们发现，人类白细胞抗原（HLA）-DR（-）或CD38（-）的新鲜CD34（+）Lin（-）细胞组成性表达GATA-3，但不表达T细胞因子-1（TCF-1）或Id-3。与小鼠胎肝细胞系AFT024及特定细胞因子共同培养能够诱导TCF-1 mRNA表达。然而，在培养的子代细胞中未发现T细胞受体基因重排。Id-3是一种对T细胞分化转录因子具有显性负功能的碱性螺旋环螺旋因子，其表达也上调，这可能解释了T细胞成熟失败的原因。为了更好地理解祖细胞来源的自然杀伤（NK）细胞之间的发育联系，我们研究了血液中循环的NK细胞亚群。通过逆转录聚合酶链反应和蛋白质免疫印迹分析发现，CD56（+明亮）而非CD56（+暗淡）NK细胞组成性表达TCF-1。在表达凝集素但不表达识别抑制性受体的免疫球蛋白I类的CD56（+明亮）细胞中发现的TCF-1异构体，与NK细胞分化培养中诱导产生的异构体相同，且与T细胞中的异构体明显不同。这些结果表明，TCF-1不靶向人类杀伤免疫球蛋白受体基因，TCF-1在循环的CD56（+明亮）NK细胞中独特表达，特定的TCF-1异构体可能在调节普通NK/T细胞祖细胞向NK细胞分化中起重要作用。
