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Updated: Aug 9, 2026

Characterization of Thymic Settling Progenitors in the Mouse Embryo Using In Vivo and In Vitro Assays
Published on: June 9, 2015
Phenotypic and functional characterization of c-kit expression during intrathymic T cell development
D I Godfrey1, A Zlotnik, T Suda
1DNAX Research Institute, Palo Alto, CA 94304.
Abstract:
We have studied the expression and function of c-kit on subsets of mouse thymocytes. c-kit was primarily expressed on subpopulations of CD4-CD8-CD3- triple negative (TN) cells. The strongest c-kit expression was associated with subsets that represent the least mature TN cells, including CD44+CD25- TN, and a subpopulation of CD25+ TN. These cells were also Thy-1lo, H-2Khi TSA-1hi, HSAlo, B220-, Mac-1-, and Gr-1-. Additionally, the recently described pre-TN thymocyte population (CD4loCD3-CD8-) was also c-kit+. CD25+ TN thymocytes proliferated in the presence of IL-7 and stem cell factor (the ligand for c-kit), and this proliferation was completely inhibited in the presence of anti-c-kit. Furthermore, the addition of anti-c-kit to 2-deoxyguanosine-treated fetal thymic lobes undergoing reconstitution with fetal liver-derived precursor cells inhibited their T cell differentiation potential. These observations indicate an important role for c-kit/stem cell factor interactions during early thymocyte development.
Insights
The c-kit receptor is crucial for early T cell development in the thymus. Blocking c-kit signaling inhibits the proliferation and differentiation of immature thymocytes, highlighting its essential role.
Area of Science:
- Immunology
- Developmental Biology
Background:
- The thymus is a primary lymphoid organ responsible for T cell maturation.
- Early T cell development involves distinct stages characterized by specific cell surface markers.
Purpose of the Study:
- To investigate the expression and function of c-kit in mouse thymocyte subsets.
- To elucidate the role of c-kit signaling in early T cell development.
Main Methods:
- Flow cytometry to analyze c-kit expression on thymocyte subsets.
- In vitro proliferation assays using IL-7 and stem cell factor.
- Inhibition studies using anti-c-kit antibodies in fetal thymic organ cultures.
Main Results:
- c-kit is predominantly expressed on immature, triple-negative (TN) thymocytes, particularly CD44+CD25- and CD25+ TN subsets.
- IL-7 and stem cell factor induce proliferation of CD25+ TN thymocytes, which is inhibited by anti-c-kit.
- Blocking c-kit in fetal thymic organ cultures impairs T cell differentiation from precursor cells.
Conclusions:
- c-kit signaling is essential for the proliferation and differentiation of early thymocyte progenitors.
- The c-kit/stem cell factor pathway plays a critical role in T cell development within the thymus.
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