Garbe Annette I, Krueger Andreas, Gounari Fotini, Zúñiga-Pflücker Juan Carlos, von Boehmer Harald
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
J Exp Med. 2006 Jun 12;203(6):1579-90. doi: 10.1084/jem.20060474. Epub 2006 Jun 5.
Thymic precursors expressing the pre-T cell receptor (TCR), the gammadeltaTCR, or the alphabetaTCR can all enter the CD4+ 8+ alphabeta lineage, albeit with different efficacy. Here it is shown that proliferation and differentiation of precursors with the different TCRs into alphabeta lineage cells require Notch signaling at the DN3 stage of thymic development. At the DN4 stage, Notch signaling still significantly contributes to the generation of alphabeta T cells. In particular, in alphabeta lineage commitment, the pre-TCR synergizes more efficiently with Notch signals than the other two TCRs, whereas gammadeltaTCR-expressing cells can survive and expand in the absence of Notch signals, even though Notch signaling enhances their proliferation. These observations suggest a new model of alphabeta versus gammadelta lineage choice in which lineage fate is determined by the extent of synergy between TCR and Notch signaling and in which the evolutionarily recent advent of the cell-autonomously signaling pre-TCR increased the efficacy of alphabeta T cell generation.
表达前T细胞受体（TCR）、γδTCR或αβTCR的胸腺前体细胞都可以进入CD4+8+αβ谱系，尽管效率不同。本文表明，具有不同TCR的前体细胞增殖并分化为αβ谱系细胞需要在胸腺发育的DN3阶段进行Notch信号传导。在DN4阶段，Notch信号传导仍然对αβT细胞的产生有显著贡献。特别是，在αβ谱系定向分化过程中，前TCR与Notch信号的协同作用比其他两种TCR更有效，而表达γδTCR的细胞在没有Notch信号的情况下也能存活和扩增，尽管Notch信号传导会增强它们的增殖。这些观察结果提示了一种αβ与γδ谱系选择的新模型，其中谱系命运由TCR与Notch信号传导之间的协同程度决定，并且在进化上较新出现的细胞自主信号传导前TCR提高了αβT细胞产生的效率。
