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Functional analysis of Mel-14+ and Mel-14- early precursor cells in the adult mouse thymus
1Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Abstract:
The earliest T-cell precursor population in the adult mouse thymus (low CD4 precursors) may be divided into 85% of cells expressing surface Mel-14 (LECAM-1, the lymphocyte homing receptor) and 15% of cells which are Mel-14. To date, this is the only surface marker for which we have found this population to be heterogeneous. The precursor activity of the Mel-14+ and Mel-14- subpopulation was assessed by both intrathymic and intravenous transfer of sorted cells into Ly5 congenic irradiated recipient mice. On both a cell-for-cell and a total activity basis, almost all precursor activity was associated with the Mel-14+ cells. No segregation was seen between T-cell, B-cell and dendritic cell precursor activity of the low CD4 population, all activities being concentrated in the Mel-14+ fraction. This strengthens the hypothesis that one precursor cell has the potential to form all three lineages.
Insights
Early T-cell precursors in mice are heterogeneous, with most activity found in Mel-14 (lymphocyte homing receptor) positive cells. This suggests a single precursor cell can generate T-cells, B-cells, and dendritic cells.
Area of Science:
- Immunology
- Developmental Biology
- Hematopoiesis
Background:
- The earliest T-cell precursor population in adult mouse thymus, termed low CD4 precursors, exhibits heterogeneity.
- This heterogeneity is primarily defined by the expression of the surface marker Mel-14 (lymphocyte homing receptor).
Purpose of the Study:
- To investigate the precursor activity of Mel-14 positive (Mel-14+) and Mel-14 negative (Mel-14-) subpopulations within the low CD4 precursor thymocyte population.
- To determine if Mel-14 expression segregates T-cell, B-cell, and dendritic cell precursor potential.
Main Methods:
- Isolation and sorting of Mel-14+ and Mel-14- low CD4 precursor cells from adult mouse thymus.
- Intrathymic and intravenous transfer of sorted cells into Ly5 congenic irradiated recipient mice.
- Assessment of precursor activity for T-cell, B-cell, and dendritic cell lineages.
Main Results:
- Almost all T-cell precursor activity was concentrated in the Mel-14+ subpopulation, on both a cell-for-cell and total activity basis.
- No segregation of precursor activity was observed; T-cell, B-cell, and dendritic cell precursor functions were all found within the Mel-14+ fraction.
- This indicates Mel-14 expression is a key marker for multipotent hematopoietic precursors in the thymus.
Conclusions:
- The Mel-14+ subpopulation harbors the predominant T-cell precursor activity.
- The findings support the hypothesis that a single precursor cell possesses the potential to differentiate into T-cells, B-cells, and dendritic cells.
- Mel-14 serves as a crucial marker for identifying multipotent hematopoietic stem cells within the early T-cell lineage.