b-Selection Is Associated With the Onset of CD8b Chain Expression on CD41CD8aa1 Pre-T Cells During Human Intrathymic Development

T-cell precursors that undergo productive rearrangements at the T-cell receptor (TCR) b locus are selected for proliferation and further maturation, before TCRa expression, by signaling through a pre–TCR composed of the TCRb chain paired with a pre–TCRa (pTa) chain. Such a critical developmental checkpoint, known as b-selection, results in progression from CD42 CD82 double negative (DN) to CD41 CD81 double positive (DP) TCRab2 thymocytes. In contrast to mice, progression to the DP compartment occurs in humans via a CD41 CD82 intermediate stage. Here we show that the CD41 CD82 to CD41 CD81 transition involves the sequential acquisition of the a and b chains of CD8 at distinct maturation stages. Our results indicate that CD8a, but not CD8b, is expressed in vivo in a minor subset of DP TCRab2 thymocytes, referred to as CD41 CD8aa1 pre-T cells, mostly composed of resting cells lacking cytoplasmic TCRb chain (TCRbic). In contrast, expression of CD8ab heterodimers was selectively found on DP TCRab2 thymocytes that express TCRbic and are enriched for cycling cells. Interestingly, CD41 CD8aa1 pre-T cells are shown to be functional intermediates between CD41 CD82 TCRbic and CD41 CD8ab1 TCRbic thymocytes. More importantly, evidence is provided that onset of CD8b and TCRbic expression are coincident developmental events associated with acquisition of CD3 and pTa chain on the cell surface. Therefore, we propose that the CD41 CD8aa1 to CD41 CD8ab1 transition marks the key control point of pre-TCR–mediated b-selection in human T-cell development. r 1999 by The American Society of Hematology.