Macallan Derek C, Wallace Diana L, Irvine Andrew J, Asquith Becca, Worth Andrew, Ghattas Hala, Zhang Yan, Griffin George E, Tough David F, Beverley Peter C
Department of Infectious Diseases, St George's Hospital Medical School, London, GB.
Eur J Immunol. 2003 Oct;33(10):2655-65. doi: 10.1002/eji.200324295.
During acute infectious mononucleosis (AIM), large clones of Epstein-Barr virus-specific T lymphocytes are produced. To investigate the dynamics of clonal expansion, we measured cell proliferation during AIM using deuterated glucose to label DNA of dividing cells in vivo, analyzing cells according to CD4, CD8 and CD45 phenotype. The proportion of labeled CD8(+)CD45R0(+) T lymphocytes was dramatically increased in AIM subjects compared to controls (mean 17.5 versus 2.8%/day; p<0.005), indicating very rapid proliferation. Labeling was also increased in CD4(+)CD45R0(+) cells (7.1 versus 2.1%/day; p<0.01), but less so in CD45RA(+) cells. Mathematical modeling, accounting for death of labeled cells and changing pool sizes, gave estimated proliferation rates in CD8(+)CD45R0(+) cells of 11-130% of cells proliferating per day (mean 47%/day), equivalent to a doubling time of 1.5 days and an appearance rate in blood of about 5 x 10(9) cells/day (versus 7 x 10(7) cells/day in controls). Very rapid death rates were also observed amongst labeled cells (range 28-124, mean 57%/day),indicating very short survival times in the circulation. Thus, we have shown direct evidence for massive proliferation of CD8(+)CD45R0(+) T lymphocytes in AIM and demonstrated that rapid cell division continues concurrently with greatly accelerated rates of cell disappearance.
在急性传染性单核细胞增多症（AIM）期间，会产生大量爱泼斯坦-巴尔病毒特异性T淋巴细胞克隆。为了研究克隆扩增的动态过程，我们在AIM期间使用氘代葡萄糖标记体内分裂细胞的DNA来测量细胞增殖，根据CD4、CD8和CD45表型分析细胞。与对照组相比，AIM患者中标记的CD8(+)CD45R0(+) T淋巴细胞比例显著增加（平均每天17.5%对2.8%；p<0.005），表明增殖非常迅速。CD4(+)CD45R0(+)细胞中的标记也增加（每天7.1%对2.1%；p<0.01），但CD45RA(+)细胞中增加较少。考虑到标记细胞的死亡和细胞池大小的变化进行的数学建模得出，CD8(+)CD45R0(+)细胞的估计增殖率为每天增殖细胞的11%-130%（平均47%/天），相当于倍增时间为1.5天，血液中的出现率约为5×10⁹个细胞/天（对照组为7×10⁷个细胞/天）。在标记细胞中也观察到非常快速的死亡率（范围为28%-124%，平均57%/天），表明在循环中的存活时间非常短。因此，我们已经显示了AIM中CD8(+)CD45R0(+) T淋巴细胞大量增殖的直接证据，并证明快速细胞分裂与大大加速的细胞消失率同时持续存在。
