The role of Notch and IL-7 signaling in early thymocyte proliferation and differentiation |
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Authors: | Balciunaite Gina Ceredig Rhodri Fehling Hans-Jörg Zúñiga-Pflücker Juan-Carlos Rolink Antonius G |
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Institution: | Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Basel, Switzerland. |
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Abstract: | We have analyzed the roles of Notch and IL-7 signaling in the proliferation and differentiation of mouse progenitor thymocyte subpopulations cultured on Notch delta-like-1 ligand-expressing OP9 stromal cells. Using bulk and limiting dilution cultures, we show that DN1 and DN2 cells require both Notch and IL-7 signaling for efficient proliferation and differentiation into cytoplasmic TCRbeta and surface TCRalpha/beta and TCRgamma/delta expressing T cells. Selection for cytoplasmic TCRbeta-positive cells is dependent on preTalpha expression. Both gamma/delta and alpha/beta TCR expressing T cells arising in culture can be efficiently stimulated by anti-CD3 cross-linking, suggesting that they might be functional. The differentiation of adult, but not fetal, DN1 and DN2 thymocytes into CD4 and/or CD8 expressing cells is inhibited by IL-7. Finally, efficient proliferation and differentiation of DN3 cells requires Notch signaling and preTCR expression, but is independent of IL-7. |
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Keywords: | Notch Lymphopoiesis Progenitor cells preTCR IL‐7 |
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