Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America.
PLoS One. 2012;7(8):e43509. doi: 10.1371/journal.pone.0043509. Epub 2012 Aug 22.
Invariant natural killer T (iNKT) cells develop in the thymus and branch off from the maturation pathway of conventional T cell at the DP stage. While different stages of iNKT cellular development have been defined, the actual time that iNKT cell precursors spend at each stage is still unknown.
METHODOLOGY/PRINCIPAL FINDING: Here we report on maturation dynamics of post-selection DN iNKT cells by injecting wild-type DP(dim) thymocytes into the thymus of TCRα(-/-) mice and using the Vα14-Jα18 rearrangements as a molecular marker to follow the maturation dynamics of these cells.
CONCLUSION/SIGNIFICANCE: This study shows that the developmental dynamics of DN iNKT cells in DP(dim) are very rapid and that it takes less than 1 day to down-regulate CD4 and CD8 and become DN. These DN cells are precursors of peripheral DN iNKT cells and appear in the spleen in 1-2 days. Thymic DN iNKT residents are predominantly derived from cells that quickly return from the periphery. The expansion of a very small subset of DN iNKT precursors could also play a small role in this process. These data are an example of measuring T cell maturation in the thymus and show that the maturation dynamics of selected DN iNKT cells fall within the same general time frame as conventional αβ T cells.
不变自然杀伤 T(iNKT)细胞在胸腺中发育,并在 DP 阶段从常规 T 细胞的成熟途径分支出来。虽然已经定义了 iNKT 细胞发育的不同阶段,但 iNKT 细胞前体在每个阶段实际花费的时间仍不清楚。
方法/主要发现:在这里,我们通过将野生型 DP(dim)胸腺细胞注入 TCRα(-/-)小鼠的胸腺中,并使用 Vα14-Jα18 重排作为分子标记,来报告后选择的 DN iNKT 细胞的成熟动力学。
结论/意义:这项研究表明,DP(dim)中的 DN iNKT 细胞的发育动力学非常迅速,其下调 CD4 和 CD8 并成为 DN 所需的时间不到 1 天。这些 DN 细胞是外周 DN iNKT 细胞的前体,在 1-2 天内出现在脾脏中。胸腺内的 DN iNKT 居民主要来自快速从外周返回的细胞。一小部分 DN iNKT 前体的扩增也可能在这个过程中起很小的作用。这些数据是测量胸腺中 T 细胞成熟的一个例子,表明选择的 DN iNKT 细胞的成熟动力学与常规αβ T 细胞处于相同的大致时间范围内。