Threshold of pre-T-cell-receptor surface expression is associated with alphabeta T-cell lineage commitment.
BACKGROUND
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 alphabeta versus gammadelta 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 beta-selection and been rescued from programmed cell death. Late pre-T cells (CD25(-)CD44(-)), which had traversed the beta-selection checkpoint, expressed surprisingly heterogeneous surface levels of the pre-TCR: high levels of surface pre-TCR expression were associated with commitment to the alphabeta T-cell lineage, whereas late pre-T cells with lower levels of surface pre-TCR could develop along both the alphabeta or gammadelta 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 alphabeta 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.
Bruno
L
L
Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London, WC2A 3PX, UK. L.Bruno@icrf.icnet.uk
Scheffold
A
A
Radbruch
A
A
Owen
M J
MJ
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002462:Cell Membrane; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D018960:Hyaluronan Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2