Balciunaite Gina, Ceredig Rhodri, Fehling Hans-Jörg, Zúñiga-Pflücker Juan-Carlos, Rolink Antonius G
Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Basel, Switzerland.
Eur J Immunol. 2005 Apr;35(4):1292-300. doi: 10.1002/eji.200425822.
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.
我们分析了Notch和IL-7信号通路在培养于表达Notch Delta样-1配体的OP9基质细胞上的小鼠祖胸腺细胞亚群增殖和分化中的作用。通过大量培养和有限稀释培养，我们发现双阴性1（DN1）和双阴性2（DN2）细胞高效增殖并分化为表达细胞质TCRβ以及表面TCRα/β和TCRγ/δ的T细胞需要Notch和IL-7信号通路。对细胞质TCRβ阳性细胞的选择取决于前Tα的表达。培养中产生的表达γ/δ和α/β TCR的T细胞均可通过抗CD3交联得到有效刺激，这表明它们可能具有功能。IL-7可抑制成年而非胎儿的DN1和DN2胸腺细胞分化为表达CD4和/或CD8的细胞。最后，DN3细胞的高效增殖和分化需要Notch信号通路和前TCR表达，但与IL-7无关。
