In:
Blood, American Society of Hematology, Vol. 94, No. 10 ( 1999-11-15), p. 3491-3498
Abstract:
T-cell precursors that undergo productive rearrangements at the T-cell receptor (TCR) β locus are selected for proliferation and further maturation, before TCR expression, by signaling through a pre–TCR composed of the TCRβ chain paired with a pre–TCR (pT) chain. Such a critical developmental checkpoint, known as β-selection, results in progression from CD4−CD8− double negative (DN) to CD4+CD8+ double positive (DP) TCRβ−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 β chains of CD8 at distinct maturation stages. Our results indicate that CD8, but not CD8β, is expressed in vivo in a minor subset of DP TCRβ− thymocytes, referred to as CD4+CD8+ pre-T cells, mostly composed of resting cells lacking cytoplasmic TCRβ chain (TCRβic). In contrast, expression of CD8β heterodimers was selectively found on DP TCRβ− thymocytes that express TCRβicand are enriched for cycling cells. Interestingly, CD4+CD8+ pre-T cells are shown to be functional intermediates between CD4+ CD8−TCRβic− and CD4+CD8β+ TCRβic+thymocytes. More importantly, evidence is provided that onset of CD8β and TCRβic 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+CD8β+ transition marks the key control point of pre-TCR–mediated β-selection in human T-cell development.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood.V94.10.3491.422k30_3491_3498
Language:
English
Publisher:
American Society of Hematology
Publication Date:
1999
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
