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

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Objective. 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. Materials and Methods. Transcription factor expression in fresh and cultured adult human bone marrow and umbilical cord blood progenitors was evaluated. Results. 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. Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)499-506
Number of pages8
JournalExperimental Hematology
Issue number4
StatePublished - 2001

Bibliographical note

Funding Information:
We are indebted to Valarie McCullar and Jeanne Lund for their excellent technical assistance with cell isolation and culture and to Brad Anderson for flow cytometry. This work was supported in part by National Institutes of Health Grants R01-HL-55417 and PO1-CA-65493 and in part by Grant M01-RR00400 from the National Center for Research Resources.


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