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J. Exp. Med.,
Volume 188, Number 8, October 19, 1998 1401-1412
Pre-T Cells as Immediate Precursors of
T Cell Receptor /
+ Thymocytes
By
From the * Centro de Biología Molecular "Severo Ochoa," and the During thymocyte development, progression from T cell receptor (TCR) Departamento de Inmunología y
Oncología, Centro Nacional de Biotecnología, Universidad Autónoma de Madrid, Cantoblanco,
28049 Madrid, Spain
to TCR
rearrangement is mediated by a CD3-associated pre-TCR composed of the TCR chain paired
with pre-TCR (pT). A major issue is how surface expression of the pre-TCR is regulated during normal thymocyte development to control transition through this checkpoint. Here,
we show that developmental expression of pT is time- and stage-specific, and is confined in
vivo to a limited subset of large cycling human pre-T cells that coexpress low density CD3.
This restricted expression pattern allowed the identification of a novel subset of small CD3
thymocytes lacking surface pT, but expressing cytoplasmic TCR, that represent late noncycling pre-T cells in which recombination activating gene reexpression and downregulation
of T early transcription are coincident events associated with cell cycle arrest, and immediately preceding TCR gene expression. Importantly, thymocytes at this late pre-T cell stage
are shown to be functional intermediates between large pT+ pre-T cells and TCR/+ thymocytes. The results support a developmental model in which pre-TCR-expressing pre-T
cells are brought into cycle, rapidly downregulate surface pre-TCR, and finally become small
resting pre-T cells, before the onset of TCR gene expression.
;
noncycling;
recombination activating gene;
T early
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