ALPHA-BETA AND GAMMA-DELTA T-CELLS CAN SHARE A LATE COMMON PRECURSOR
ALPHA-BETA AND GAMMA-DELTA T-CELLS CAN SHARE A LATE COMMON PRECURSOR
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DOI：
10.1016/s0960-9822(95)00131-x
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发表时间：
1995-06-01
期刊：
影响因子：
9.2
通讯作者：
HAYDAY, AC
中科院分区：
文献类型：
--
作者：
DUDLEY, EC;GIRARDI, M;HAYDAY, AC
背景：在整个脊椎动物发育过程中，T细胞细分为α β和γ δ亚型是保守的。分别的α - β和γ - δ t细胞受体（tcr）是由体细胞重排基因编码的。对于单个胸腺细胞是否可以成为γ δ T细胞或α β T细胞作为随机基因重排过程的结果，或者这两种类型的T细胞是否来自不同的谱系，人们一直有广泛的猜测。然而，许多实验结果显然是相互矛盾的，而且这个问题——免疫学和发育中的一个基本问题——仍然没有得到解决。结果：为了解决这个问题，我们使用了最近开发的聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术，该技术使我们能够定量地检查出生后α β T细胞及其祖细胞中TCR γ和δ基因的状态。有趣的是，这样的细胞缺乏有效重排的δ和γ基因，它们可以编码δ和γ TCR多肽链。然而，在可以重排TCR δ基因片段，但TCR δ基因在其他方面没有功能的小鼠中，没有看到这种生产性重排的消耗。结论：我们获得的定量数据符合随机假设的预测：即祖T细胞首先尝试成为γ δ T细胞，如果不成功，则尝试成为crp T细胞。因此，α - β和γ - δ T细胞可以来源于一个共同的前体胸腺细胞。因此，在最简单的情况下，谱系决定因素是在TCR α基因重排发生之前γ和δ基因的成功重排，这导致TCR δ基因座的缺失，从而阻止进一步的γ δ t细胞分化。相比之下，TCR β位点的成功重排与细胞成为γ - δ或α - β T细胞保持兼容。
Background: The subdivision of T cells into alpha beta and gamma delta subtypes is conserved throughout vertebrate development. The respective alpha beta and gamma delta T-cell receptors (TCRs) are encoded by somatically rearranged genes. There has been broad speculation as to whether an individual thymocyte can become either a gamma delta T cell or an alpha beta T cell as a result of stochastic gene rearrangement processes, or whether the two types of T cell are derived from separate lineages. Many of the experimental findings are apparently conflicting, however, and the issue - a basic one in immunology and development - remains unresolved.Results: To address this issue, we have used the recently developed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, which allows us to examine quantitatively the status of TCR gamma and delta genes in postnatal alpha beta T cells and their progenitors. Interestingly, such cells are depleted of productively rearranged delta and gamma genes, which can encode delta and gamma TCR polypeptide chains. However, in mice that can rearrange TCR delta gene segments, but in which the TCR delta gene is non-functional in other respects, no such depletion of productive rearrangements is seen.Conclusion: The quantitative data that we have obtained fulfill the predictions of the stochastic hypothesis: that is, a progenitor T cell first attempts to become a gamma delta T cell and, if unsuccessful, then attempts to become an crp T cell. Thus, alpha beta and gamma delta T cells can derive from a common precursor thymocyte. In the simplest case, therefore, lineage-determining factors are the successful rearrangement of both gamma and delta genes before TCR alpha gene rearrangements occur, which lead to deletion of the TCR delta locus and thereby preclude further gamma delta T-cell differentiation. In contrast, successful rearrangement of the TCR beta locus remains compatible with cells becoming either gamma delta or alpha beta T cells.