Jabbari Ali, Harty John T
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
J Exp Med. 2006 Apr 17;203(4):919-32. doi: 10.1084/jem.20052237. Epub 2006 Mar 27.
The formation of memory CD8 T cells is an important goal of vaccination. However, although widespread use of booster immunizations in humans generates secondary and tertiary CD8 T cell memory, experimental data are limited to primary CD8 T cell memory. Here, we show that, compared with primary memory CD8 T cells, secondary memory CD8 T cells exhibit substantially delayed conversion to a central-memory phenotype, as determined by CD62L expression and interleukin (IL)-2 production. This delayed conversion to a central-memory phenotype correlates with reduced basal proliferation and responsiveness to IL-15, although in vitro coculture with a high concentration of IL-15 is capable of inducing proliferation and CD62L upregulation. Functionally, secondary memory CD8 T cells are more protective in vivo on a per cell basis, and this may be explained by sustained lytic ability. Additionally, secondary memory CD8 T cells are more permissive than primary memory CD8 T cells for new T cell priming in lymph nodes, possibly suggesting a mechanism of replacement for memory T cells. Thus, primary and secondary memory CD8 T cells are functionally distinct, and the number of encounters with antigen influences memory CD8 T cell function.
记忆性CD8 T细胞的形成是疫苗接种的一个重要目标。然而，尽管人类广泛使用加强免疫可产生二级和三级CD8 T细胞记忆，但实验数据仅限于一级CD8 T细胞记忆。在此，我们表明，与一级记忆性CD8 T细胞相比，二级记忆性CD8 T细胞向中央记忆表型的转化显著延迟，这是通过CD62L表达和白细胞介素（IL）-2产生来确定的。这种向中央记忆表型的延迟转化与基础增殖减少和对IL-15的反应性降低相关，尽管与高浓度IL-15进行体外共培养能够诱导增殖和CD62L上调。在功能上，二级记忆性CD8 T细胞在体内单个细胞基础上具有更强的保护作用，这可能是由持续的裂解能力所解释的。此外，二级记忆性CD8 T细胞在淋巴结中比一级记忆性CD8 T细胞对新的T细胞启动更具耐受性，这可能暗示了记忆性T细胞的一种替代机制。因此，一级和二级记忆性CD8 T细胞在功能上是不同的，与抗原接触的次数会影响记忆性CD8 T细胞的功能。
