Threshold of pre-T-cell-receptor surface expression is associated with αβ T-cell lineage commitment

AbstractBackground: The development of immature thymocytes is regulated by the pre-T-cell receptor (pre-TCR). The pre-TCR is involved in several developmental processes including rescuing cells from programmed cell death, allelic exclusion and αβ versus γδ T-cell lineage commitment. A major issue is how the pre-TCR functions to integrate these processes in developing thymocytes.Results: We have used a sensitive immunofluorescence technique to reveal the surface-expression profile of the pre-TCR on immature thymocyte subsets. We show that early pre-T cells (CD25+CD44−) can be subdivided on the basis of the level of surface pre-TCR expression. Detectable surface pre-TCR expression identified a rapidly cycling population of early pre-T cells which had successfully undergone β-selection and been rescued from programmed cell death. Late pre-T cells (CD25−CD44−), which had traversed the β-selection checkpoint, expressed surprisingly heterogeneous surface levels of the pre-TCR: high levels of surface pre-TCR expression were associated with commitment to the αβ T-cell lineage, whereas late pre-T cells with lower levels of surface pre-TCR could develop along both the αβ or γδ T-cell lineages.Conclusions: These data demonstrate that the surface expression of the pre-TCR can be used to reveal newly identified stages of T-cell development and to provide insights into αβ T-cell lineage commitment. They show that, although pre-TCR expression does not act as a developmental switch per se, its level of surface expression on late pre-T cells predicts their developmental potential