T-cell factor-1 expression during human natural killer cell development and in circulating CD56(+) bright natural killer cells

Objective. Transcription factors are essential to govern differentiation al ong the lymphoid lineage from uncommitted hematopoietic stem cells. Althoug h many of these transcription factors have putative roles based on murine k nockout experiments, their function in human lymphoid development is less k nown and was studied further. Materials and Methods. Transcription factor expression in fresh and culture d adult human bone marrow and umbilical cord blood progenitors was evaluate d. Results. We found that fresh CD34(+)Lin(-) cells that are human leukocyte a ntigen (HLA)-DR- or CD38(-) constitutively express GATA-3 but not T-cell fa ctor-1 (TCF-1) or Id-3. Culture with the murine fetal liver cell line AFT02 4 and defined cytokines was capable of inducing TCF-1 mRNA. However, no T-c ell receptor gene rearrangement was identified in cultured progeny. Id-3, a basic helix loop helix factor with dominant negative function for T-cell d ifferentiation 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 cel ls constitutively express TCF-1 by reverse transcriptase polymerase chain r eaction and Western blot analysis. The TCF-1 isoform found in CD56(+bright) cells, which express lectin but not immunoglobulin class I recognizing inh ibitory receptors, was identical to that induced in NK cell differentiation culture and was distinctly different from isoforms in T cells. Conclusions. These results suggest that TCF-1 does not target human killer immunoglobulin receptor genes, TCF-1 is uniquely expressed in circulating C D56(+bright) NK cells, and specific TCF-1 isoforms may play an important ro le in regulating NK differentiation from a common NK/T-cell progenitor. (C) 2001 International Society for Experimental Hematology. Published by Elsev ier Science Inc.