Murray John M, Kaufmann Gilbert R, Hodgkin Philip D, Lewin Sharon R, Kelleher Anthony D, Davenport Miles P, Zaunders John J
School of Mathematics, University of NSW, Sydney, Australia.
Immunol Cell Biol. 2003 Dec;81(6):487-95. doi: 10.1046/j.1440-1711.2003.01191.x.
Analysing T-cell receptor excision circle numbers in healthy individuals we find a marked change in the source of naive T cells before and after 20 years of age. The bulk of the naive T cell pool is sustained primarily from thymic output for individuals younger than 20 years of age whereas proliferation within the naive phenotype is dominant for older individuals. Over 90% of phenotypically naive T cells in middle age are not of direct thymic origin. Moreover, this change in source of naive T cells is accompanied either by an increased death rate of T cells from the thymus or reduced thymic export. Modelling of these processes shows that new naive T cells of a thymic origin have a half-life of approximately 50 days before this change occurs, and that either the life-span of recent thymic emigrants (but not necessarily of all naive cells) decreases approximately threefold in middle age, or thymic production drops by this same amount. The decay rate of T-cell receptor excision circle levels for individuals over 20 years of age is consistent with the decay rate of the productive thymus. Our modelling suggests that at age 25, thymic export is responsible for 20% of naive T-cell production and that this percentage decreases with the 15.7 year half-life of the productive thymus so that by age 55 only 5% of naive production arises from thymic export.
通过分析健康个体的T细胞受体切除环数量，我们发现20岁前后初始T细胞的来源有显著变化。对于20岁以下的个体，初始T细胞库的主体主要由胸腺输出维持，而对于年龄较大的个体，初始表型内的增殖占主导。中年时，超过90%的表型初始T细胞并非直接来源于胸腺。此外，初始T细胞来源的这种变化伴随着胸腺来源的T细胞死亡率增加或胸腺输出减少。对这些过程的建模显示，在这种变化发生之前，胸腺来源的新初始T细胞的半衰期约为50天，并且在中年时，近期胸腺移民（但不一定是所有初始细胞）的寿命大约缩短了三倍，或者胸腺产量下降了相同幅度。20岁以上个体的T细胞受体切除环水平的衰减率与有功能的胸腺的衰减率一致。我们的模型表明，在25岁时，胸腺输出占初始T细胞产生的20%，并且随着有功能的胸腺的15.7年半衰期，这一百分比会下降，以至于到55岁时，只有5%的初始细胞产生来自胸腺输出。
