1: Hum Cell. 2004 Jun;17(2):85-92. 

Transcription factor expression in cell lines derived from natural killer-cell
and natural killer-like T-cell leukemia-lymphoma.

Matsuo Y, Drexler HG, Harashima A, Okochi A, Shimizu N, Orita K.

Fujisaki Cell Center, Hayashibara Biochemical Labs, Okayama 702-8006, Japan.
yomatsuo@hayashibara.co.jp

Although a number of transcription factors (TFs) have been identified that play
a pivotal role in the development of hematopoietic lineages, only little is
known about factors that may influence development and lineage commitment of
natural killer (NK) or NK-like T (NKT)-cells. Obviously to fully appreciate the
NK- and NKT-cell differentiation process, it is important to identify and
characterize the TFs effecting the NK- and NKT-cell lineage. Furthermore, these
TFs may play a role in NK- or NKT-cell leukemias, in which the normal
differentiation program is presumably disturbed. The present study analyzed the
expression of the following 13 TFs: AML1, CEBPA, E2A, ETS1, GATA1, GATA2, GATA3,
IKAROS, IRF1, PAX5, PU1, TBET and TCF1 in 7 malignant NK-cell lines together
with 5 malignant NKT-cell lines, 5 T-cell acute lymphoblastic leukemia (ALL)
cell lines including 3 gamma/delta T-cell receptor (TCR) type and 2 alpha/beta
TCR type, and 3 B-cell precursor (BCP) leukemia cell lines. AML1, E2A, ETS1,
IKAROS and IRF1 were found to be positive for all cell lines tested whereas
GATA1 turned out to be universally negative. CEBPA, PAX5 and PU1 were negative
for all cell lines tested except in the three positive BCP-cell lines. GATA2 was
positive for 3/5 T-cell lines but negative for the other cell lines. GATA3 was
positive for 7/7 NK-, 4/5 NKT-, 5/5 T- and 2/3 BCP-cell lines. TBET was positive
for all NK- and NKT-cell lines and negative for all T- and BCP-cell lines except
one BCP-cell line. In contrast to the expression of TBET, TCF1 was negative for
all NK- and NKT-cell lines, being positive for 4/5 T- and 1/3 BCP-cell lines.
Expression analysis of TFs revealed that NK- and NKT-cell lines showed identical
profiles, clearly distinct from those of the other T-ALL or BCP-ALL
leukemia-derived cell lines..

PMID: 15369140 [PubMed - indexed for MEDLINE]


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2: J Immunol. 2004 Sep 15;173(6):3935-44. 

Analysis of Notch1 function by in vitro T cell differentiation of Pax5 mutant
lymphoid progenitors.

Hoflinger S, Kesavan K, Fuxa M, Hutter C, Heavey B, Radtke F, Busslinger M.

Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.

Signaling through the Notch1 receptor is essential for T cell development in the
thymus. Stromal OP9 cells ectopically expressing the Notch ligand Delta-like1
mimic the thymic environment by inducing hemopoietic stem cells to undergo in
vitro T cell development. Notch1 is also expressed on Pax5-/- pro-B cells, which
are clonable lymphoid progenitors with a latent myeloid potential. In this
study, we demonstrate that Pax5-/- progenitors efficiently differentiate in
vitro into CD4+CD8+ alphabeta and gammadelta T cells upon coculture with
OP9-Delta-like1 cells. In vitro T cell development of Pax5-/- progenitors
strictly depends on Notch1 function and progresses through normal developmental
stages by expressing T cell markers and rearranging TCRbeta, gamma, and delta
loci in the correct temporal sequence. Notch-stimulated Pax5-/- progenitors
efficiently down-regulate the expression of B cell-specific genes, consistent
with a role of Notch1 in preventing B lymphopoiesis in the thymus. At the same
time, Notch signaling rapidly induces cell surface expression of the c-Kit
receptor and transcription of the target genes Deltex1 and pre-Talpha
concomitant with the activation of TCR Vbeta germline transcription and the
regulatory genes GATA3 and Tcf1. These data suggest that Notch1 acts upstream of
GATA3 and Tcf1 in early T cell development and regulates Vbeta-DJbeta
rearrangements by controlling the chromatin accessibility of Vbeta genes at the
TCRbeta locus. Copyright 2004 The American Association of Immunologists, Inc.

PMID: 15356142 [PubMed - indexed for MEDLINE]


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3: Annu Rev Immunol. 1999;17:149-87. 

Transcriptional regulation of T lymphocyte development and function.

Kuo CT, Leiden JM.

Department of Medicine, University of Chicago, Illinois 60637, USA.

The development and function of T lymphocytes are regulated tightly by signal
transduction pathways that include specific cell-surface receptors,
intracellular signaling molecules, and nuclear transcription factors. Since
1988, several families of functionally important T cell transcription factors
have been identified. These include the Ikaros, LKLF, and GATA3 zinc-finger
proteins; the Ets, CREB/ATF, and NF-kappa B/Rel/NFAT transcription factors; the
Stat proteins; and HMG box transcription factors such as LEF1, TCF1, and Sox4.
In this review, we summarize our current understanding of the transcriptional
regulation of T cell development and function with particular emphasis on the
results of recent gene targeting and transgenic experiments. In addition to
increasing our understanding of the molecular pathways that regulate T cell
development and function, these results have suggested novel targets for genetic
and pharmacological manipulation of T cell immunity.

Publication Types:
    Review

PMID: 10358756 [PubMed - indexed for MEDLINE]


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