Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 35, Issue 4, Pages 1292-1300Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.200425822
Keywords
notch; lymphopoiesis; progenitor cells; preTCR; IL-7
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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 TCRP and surface TCR alpha/beta and TCR gamma/delta expressing T cells. Selection for cytoplasmic TCRP-positive cells is dependent on preT alpha 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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