Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales, Australia.
Immunol Cell Biol. 2010 Feb;88(2):157-64. doi: 10.1038/icb.2009.80. Epub 2009 Oct 27.
Acute infection leads to CD8(+) T-cell activation, division and differentiation. Following clearance of infection, cells revert to two distinct subsets of memory, central (T(CM)) and effector (T(EM)) memory. Adoptive transfer of naive T-cell receptor transgenic (TCR-tg) T cells has been used to study the differentiation of these memory subsets, which are often discriminated by expression of CD62L. Naive CD8(+) T cells are CD62L(high), and CD62L expression is lost during the 'effector' phase. Adoptive transfer studies show that higher transfer frequencies result in diminished T-cell expansion and a higher proportion CD62L(high). This suggests a relationship between CD62L expression and cell division, where division leads to conversion from CD62L(high) to CD62L(low) phenotype. To address this hypothesis we adoptively transferred graded numbers of OT-1 TCR-tg T cells from naive donors and tracked the kinetics and phenotype of the immune response after infection. We developed a simple mathematical model of division-linked CD62L differentiation, which we compared with the experimental data. Our results show that division-linked differentiation predicts the differences in proportion of cells CD62L(high) observed between responses of different adoptive transfer number and within individual mice. We calculate that approximately 20% of CD62L(high) cells convert to CD62L(low) during each division.
急性感染会导致 CD8(+)T 细胞的激活、分裂和分化。感染清除后，细胞恢复为两种不同的记忆亚群，中央记忆 (T(CM)) 和效应记忆 (T(EM))。幼稚 T 细胞受体转基因 (TCR-tg)T 细胞的过继转移已被用于研究这些记忆亚群的分化，这些亚群通常通过 CD62L 的表达来区分。幼稚 CD8(+)T 细胞 CD62L(高)，CD62L 表达在“效应”阶段丢失。过继转移研究表明，更高的转移频率导致 T 细胞扩增减少和更高比例的 CD62L(高)。这表明 CD62L 表达与细胞分裂之间存在关系，其中分裂导致从 CD62L(高)到 CD62L(低)表型的转换。为了验证这一假设，我们从幼稚供体过继转移了不同数量的 OT-1 TCR-tgT 细胞，并在感染后跟踪免疫反应的动力学和表型。我们建立了一个与实验数据相比较的基于分裂的 CD62L 分化的简单数学模型。我们的结果表明，基于分裂的分化预测了不同过继转移数量的反应之间以及单个小鼠内观察到的 CD62L(高)细胞比例的差异。我们计算出大约 20%的 CD62L(高)细胞在每次分裂中转化为 CD62L(低)。
