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ß T Cell Lineage Commitment and Differentiation1
Centre d’Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique, Marseille, France
T cell differentiation in the mouse thymus is an intricate, highly
coordinated process that requires the assembly of TCR complexes from
individual components, including those produced by the precisely timed
V(D)J recombination of TCR genes. Mice carrying a homozygous deletion
of the TCRß transcriptional enhancer (Eß) demonstrate an inhibition
of V(D)J recombination at the targeted TCRß locus and a block in
ß T cell differentiation. In this study, we have characterized the
T cell developmental defects resulting from the
Eß-/- mutation, in light of previously
reported results of the analyses of TCRß-deficient
(TCRß-/-) mice. Similar to the latter mice,
production of TCRß-chains is abolished in the
Eß-/- animals, and under these conditions
differentiation into cell-surface TCR-,
CD4+CD8+ double positive (DP) thymocytes
depends essentially on the cell-autonomous expression of TCR
-chains
and, most likely, TCR
-chains. However, contrary to previous reports
using TCRß-/- mice, a minor population of
TCR + DP thymocytes was found within the
Eß-/- thymi, which differ in terms of T
cell-specific gene expression and V(D)J recombinase activity, from the
majority of TCR-, ß lineage-committed DP thymocytes.
We discuss these data with respect to the functional role of Eß in
driving ß T cell differentiation and the mechanism of ß T
lineage commitment.
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