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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3491-3498
 -Selection Is Associated With the Onset of CD8 Chain Expression
on CD4+CD8 + Pre-T Cells During Human
Intrathymic Development
Yolanda R. Carrasco,
César Trigueros,
Almudena R. Ramiro,
Virginia G. de Yébenes, and
María L. Toribio
From the Centro de Biología Molecular "Severo Ochoa,"
Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
T-cell precursors that undergo productive rearrangements at the
T-cell receptor (TCR)  locus are selected for proliferation and
further maturation, before TCR expression, by signaling through a
pre-TCR composed of the TCR chain paired with a pre-TCR (pT) chain. Such a critical developmental checkpoint, known as
-selection, results in progression from CD4
CD8 double negative (DN) to CD4+
CD8+ double positive (DP) TCR
thymocytes. In contrast to mice, progression to the DP compartment occurs in humans via a CD4+ CD8
intermediate stage. Here we show that the CD4+
CD8 to CD4+ CD8+ transition
involves the sequential acquisition of the and chains of CD8 at
distinct maturation stages. Our results indicate that CD8, but not
CD8, is expressed in vivo in a minor subset of DP
TCR thymocytes, referred to as CD4+
CD8+ pre-T cells, mostly composed of resting cells
lacking cytoplasmic TCR chain (TCRic). In contrast,
expression of CD8 heterodimers was selectively found on DP
TCR thymocytes that express TCRic
and are enriched for cycling cells. Interestingly, CD4+
CD8+ pre-T cells are shown to be functional
intermediates between CD4+ CD8
TCRic and CD4+
CD8+ TCRic+
thymocytes. More importantly, evidence is provided that onset of CD8
and TCRic expression are coincident developmental events associated with acquisition of CD3 and pT chain on the cell surface. Therefore, we propose that the CD4+
CD8+ to CD4+
CD8+ transition marks the key control point of
pre-TCR-mediated -selection in human T-cell development.
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