The authors had previously shown that cell-surface CD27 distinguishes between cells undergoing T- and B-cell development. In this study, they set out to examine CD27 expression at the various stages of T-cell development. At the double-negative 3 (DN3) stage of development — at which cells complete commitment to the T-cell lineage, rearrange T-cell receptor (TCR) gene loci to generate functional TCR chains (the first main checkpoint in T-cell development), and become committed to the αβ or γδ T-cell lineage — cells could be divided into two populations on the basis of CD27 expression: CD27low cells (denoted DN3a cells) and CD27hi cells (denoted DN3b cells). The authors showed that DN3a cells can give rise to DN3b cells and that the upregulation of CD27 expression marks the transition between cells that are committed to the T-cell lineage but have not passed the developmental checkpoint at which successful rearrangement of TCR gene loci is tested (that is, DN3a cells) and cells that have passed this checkpoint and are committed to become either αβ or γδ T cells (that is, DN3b cells).
The identification of CD27 as a marker for the earliest αβ and γδ T-lineage cells allowed the authors to purify and characterize these populations. Analysis of gene-expression programmes showed differential regulation of various factors. The ratio of mRNA encoding the anti-apoptotic proteins BCL-2 (B-cell lymphoma 2) to BCL-XL was found to be markedly lower in αβ T-lineage cells than in γδ T-lineage cells. In addition, mRNA encoding the transcription factors EGR2 (early growth response 2) and EGR3 was detectable only in γδ T-lineage cells, and the two lineages also showed differential expression of several other transcription factors: RUNX3 (runt-related transcription factor 3), HEB (HeLa E-box-binding protein) and some Ikaros-family members.
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