Laboratory of Lymphocyte Biology, Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Curr Opin Immunol. 2010 Apr;22(2):185-92. doi: 10.1016/j.coi.2009.12.006. Epub 2010 Jan 13.
Alphabeta and gammadelta T cells develop in the thymus from a common precursor. Although lineages initially were defined by the type of TCR they express, it soon became clear that the TCR type per se does not play a deterministic role in the lineage decision, since in various transgenic and knockout models, as well as in a small fraction of cells in wt mice, the TCRgammadelta can drive the differentiation of alphabeta lineage cells and the TCRalphabeta can drive differentiation of gammadelta lineage cells. Thus until recently it was unclear what determines lineage choice and at which stage the two lineages diverge. Recent observations suggest that TCR signal strength determines lineage fate and that lineage choice is made at or shortly after the first TCR-controlled checkpoint. While it is clear that the decision between alphabeta and gammadelta lineages is made at the first TCR-controlled checkpoint and the alphabeta sublineages split off later, it is less clear whether gammadelta sublineages divert already at the first TCR-controlled checkpoint or later. Recent experiments support the former view.
alphabeta 和 gammadelta T 细胞从共同前体在胸腺中发育。尽管谱系最初是根据它们表达的 TCR 类型来定义的，但很快就清楚了，TCR 类型本身并不能在谱系决定中起决定性作用，因为在各种转基因和敲除模型中，以及在 wt 小鼠的一小部分细胞中，TCRgammadelta 可以驱动 alphabeta 谱系细胞的分化，而 TCRalphabeta 可以驱动 gammadelta 谱系细胞的分化。因此，直到最近，什么决定谱系选择以及两个谱系在哪个阶段分化仍不清楚。最近的观察表明，TCR 信号强度决定谱系命运，并且谱系选择是在第一个 TCR 控制的检查点或之后不久做出的。虽然很清楚，alphabeta 和 gammadelta 谱系之间的决定是在第一个 TCR 控制的检查点做出的，并且 alphabeta 亚谱系稍后分离，但不太清楚 gammadelta 亚谱系是否已经在第一个 TCR 控制的检查点或之后发生转变。最近的实验支持前一种观点。
