Expression of IL-7 receptor α is necessary but not sufficient for the formation of memory CD8 T cells during viral infection
Expression of IL-7 receptor α is necessary but not sufficient for the formation of memory CD8 T cells during viral infection
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DOI：
10.1073/pnas.0705007104
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发表时间：
2007-07-10
影响因子：
11.1
通讯作者：
Kaech, Susan M.
中科院分区：
文献类型：
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作者：
Hand, Timothy W.;Morre, Michel;Kaech, Susan M.
在许多急性病毒和细菌感染期间，IL-7受体α链（IL-7R α）在效应CD8 T细胞的亚群上表达，所述效应CD8 T细胞优先发育成长寿命记忆CD8 T细胞。这些细胞在功能上需要IL-7R α，但目前尚不清楚IL-7R α是否主要用于诱导其分化为记忆细胞或维持其长期存活。为了研究这个问题，在病毒感染期间，IL-7 R α在所有抗原特异性效应CD 8 T细胞上组成性过表达。组成性IL-7R α表达对形成的效应和记忆CD8 T细胞的数量或功能的影响最小。这表明IL-7R α表达不足以驱动记忆细胞发育。特别地，强制的IL-7R α表达不能拯救短寿命效应CD8 T细胞中的杀伤细胞凝集素样受体G1（KLRG1）免于死亡，表明大多数效应CD8 T细胞以IL-7R α非依赖性方式死亡。此外，我们发现，无论IL-7 R α的异位表达如何，KLIRG1（hi）而不是KLRG1（10）效应CD8 T细胞都不能很好地增殖为IL-7，这可能是由于KLIRG1（hi）细胞中p27（kip）的量增加。由于IL-7可以使p27（kip）不稳定，因此该结果表明KILRG1（hi）和KLRG1（lo）效应CD8 T细胞在传递IL-7信号的能力方面天然不同。总之，这些结果揭示IL-7R α表达对于记忆性CD8 T细胞的产生是允许的，但不是指导性的。
During many acute viral and bacterial infections, IL-7 receptor alpha-chain (IL-7R alpha) is expressed on a subset of effector CD8 T cells that preferentially develop into long-lived memory CD8 T cells. These cells functionally require IL-7R alpha, but it is unclear whether IL-7R alpha acts mainly to induce their differentiation into memory cells or to sustain their long-term survival. To examine this question, IL-7R alpha was constitutively overexpressed on all antigen-specific effector CD8 T cells during viral infection. Constitutive IL-7R alpha expression had minimal effects on the numbers or function of effector and memory CD8 T cells formed. This indicated that IL-7R alpha expression is not sufficient to drive memory cell development. In particular, the forced IL-7R alpha expression did not rescue the killer cell lectin-like receptor G1 (KLRG1)hi short-lived effector CD8 T cells from death, showing that the majority of effector CD8 T cells die in an IL-7R alpha-independent manner. Moreover, we found that, regardless of the ectopic expression of IL-7R alpha, the KLIRG1(hi), but not the KLRG1(10) effector CD8 T cells, were unable to proliferate well to IL-7, which may be due to increased amounts of p27(kip) in KLIRG1(hi) cells. Because IL-7 can destabilize p27(kip), this result suggested that KILRG1(hi) and KLRG1(lo) effector CD8 T cells naturally differ in their ability to transmit IL-7 signals. Altogether, these results reveal that IL-7R alpha expression is permissive, but not instructive, to the creation of memory CD8 T cells.