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Published on: December 7, 2015
T cell receptor-instructed alphabeta versus gammadelta lineage commitment revealed by single-cell analysis
Taras Kreslavsky1, Annette I Garbe, Andreas Krueger
1Laboratory of Lymphocyte Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
The Journal of Experimental Medicine
|April 30, 2008
Summary
T-cell development commitment occurs after T-cell receptor (TCR) expression, not before. TCR signaling strength, not prior commitment, determines whether T-cells become alphabeta or gammadelta lineages.
Area of Science:
- Immunology
- Developmental Biology
- T-cell biology
Background:
- Alphabeta and gammadelta T cells originate from a common thymic precursor.
- The timing of lineage commitment and the role of T-cell receptor (TCR) signaling remain unclear.
- Existing models propose commitment occurs either before or after TCR expression.
Purpose of the Study:
- To determine the stage of lineage commitment for alphabeta and gammadelta T cells.
- To investigate the precise role of TCR signaling in T-cell lineage fate determination.
- To differentiate between proposed models of T-cell commitment.
Main Methods:
- Single T-cell precursor fate tracing.
- In vivo lineage commitment analysis.
- Modulation of TCR signaling pathways.
Main Results:
- Lineage commitment to either alphabeta or gammadelta T cells occurs after TCR expression.
- TCR signaling strength directly influences lineage commitment.
- Modulating TCR signaling in progeny of a single TCR-expressing cell alters their lineage fate.
Conclusions:
- TCR expression is a prerequisite for lineage commitment.
- TCR signaling is not merely confirmatory but actively directs T-cell lineage fate.
- These findings resolve the debate on T-cell commitment timing and the role of TCR signaling.
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