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-Selection1
* Molecular Oncology Laboratory and
LRF Virus Center, Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow, United Kingdom
The development of T cells in the thymus is regulated by a series
of stage-specific transcription factors. Deregulated expression of
these factors can lead to alterations in thymocyte development with the
production of aberrant cell subsets and predispose to tumor formation.
The three genes of the Runx family are multilineage
regulators of differentiation that have been reported to be expressed
in the T cell lineage. However, their roles in thymocyte development
and T cell function are largely unknown. While the
Runx2/Cbfa1/AML3/Pebp2
a gene plays a primary role in
osteogenesis and regulates a number of key bone regulatory genes, we
show here that Runx2 is also expressed during the
earliest phase of thymic development, in the double-negative subset.
Furthermore, enforced expression of Runx2 in transgenic
mice under the CD2 promoter was found to affect T cell development at a
stage coincident with 
-selection, resulting in an expansion of
double-negative CD4 and CD8 immature single-positive cells. Unlike
wild-type controls this preselection population
(CD4-CD8+heat-stable
Ag+TCR-) is in a nonproliferative
state, but appears to be primed for further transformation events.
Overall the data suggest that Runx2 accelerates
development to the CD8 immature single-positive stage, but retards
subsequent differentiation to the double-positive stage. Thus,
Runx2 joins a small group of transcription factors that
can interfere with early T cell development, cause an expansion of a
specific subset, and predispose to lymphoma.
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