Differential sensitivity of naive and memory CD8+ T cells to apoptosis in vivo
Differential sensitivity of naive and memory CD8+ T cells to apoptosis in vivo
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DOI：
10.4049/jimmunol.169.7.3760
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发表时间：
2002-10-01
影响因子：
4.4
通讯作者：
Ahmed, R
中科院分区：
文献类型：
--
作者：
Grayson, JM;Harrington, LE;Ahmed, R
细胞凋亡是免疫系统内稳态的关键调节因子。在这项研究中，我们证明了记忆性CD 8（+）T细胞比幼稚细胞更能抵抗凋亡。小鼠全身照射后，幼稚和记忆CD 8（+）T细胞的数量均减少，但幼稚细胞数量的减少是记忆CD 8（+）T细胞的8倍。除了检测辐射诱导的细胞凋亡外，我们还分析了暴露于Ag后体内幼稚和记忆CD 8（+）T细胞的扩张和收缩。我们发现，记忆CD 8（+）T细胞不仅在病毒感染后比幼稚细胞反应更快，而且与幼稚细胞产生的初级效应细胞相比，记忆细胞产生的次级效应细胞经历的收缩要少得多（3- 5倍vs 10- 20倍减少）。在淋巴组织和非淋巴组织中均观察到次级记忆细胞数量增加。当幼稚细胞和记忆细胞被转移到同一只动物中时，次级效应细胞比初级效应细胞经历更少的收缩。这些分析同一动物中初级和次级效应物凋亡的实验明确地表明，次级反应的减小反映了记忆T细胞的内在特性，而不仅仅是由于环境影响。这些发现对设计初免/加强疫苗策略以及优化治疗慢性感染的免疫方案具有重要意义。
Apoptosis is a critical regulator of homeostasis in the immune system. In this study we demonstrate that memory CD8(+) T cells are more resistant to apoptosis than naive cells. After whole body irradiation of mice, both naive and memory CD8(+) T cells decreased in number, but the reduction in the number of naive cells was 8-fold greater than that in memory CD8(+) T cells. In addition to examining radiation-induced apoptosis, we analyzed the expansion and contraction of naive and memory CD8(+) T cells in vivo following exposure to Ag. We found that memory CD8(+) T cells not only responded more quickly than naive cells after viral infection, but that secondary effector cells generated from memory cells underwent much less contraction compared with primary effectors generated from naive cells (3- to 5-fold vs 10- to 20-fold decrease). Increased numbers of secondary memory cells were observed in both lymphoid and non-lymphoid tissues. When naive and memory cells were transferred into the same animal, secondary effectors underwent less contraction than primary effector cells. These experiments analyzing apoptosis of primary and secondary effectors in the same animal show unequivocally that decreased downsizing of the secondary response reflects an intrinsic property of the memory T cells and is not simply due to environmental effects. These findings have implications for designing prime/boost vaccine strategies and also for optimizing immunotherapeutic regimens for treatment of chronic infections.