Joshi Nikhil S, Cui Weiguo, Chandele Anmol, Lee Heung Kyu, Urso David R, Hagman James, Gapin Laurent, Kaech Susan M
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity. 2007 Aug;27(2):281-95. doi: 10.1016/j.immuni.2007.07.010.
As acute infections resolve, effector CD8(+) T cells differentiate into interleukin-7 receptor(lo) (IL-7R(lo)) short-lived effector cells (SLECs) and IL-7R(hi) memory precursor effector cells (MPECs) capable of generating long-lived memory CD8(+) T cells. By using another SLEC marker, KLRG1, we found that KLRG1(hi) effector cells began appearing early during infection and were committed to downregulating IL-7R. Unlike IL-7R(hi) MPECs, KLRG1(hi) IL-7R(lo) SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or homeostatic turnover. The decision between SLEC and MPEC fates was regulated by the amount of inflammatory cytokines (i.e., IL-12) present during T cell priming. According to the amount of inflammation, a gradient of T-bet was created in which high T-bet expression induced SLECs and low expression promoted MPECs. These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential.
随着急性感染的消退,效应性CD8(+) T细胞分化为白细胞介素-7受体低表达(IL-7R(lo))的短寿命效应细胞(SLECs)和能够产生长寿命记忆性CD8(+) T细胞的IL-7R高表达记忆前体效应细胞(MPECs)。通过使用另一种SLEC标志物KLRG1,我们发现KLRG1高表达效应细胞在感染早期就开始出现,并致力于下调IL-7R。与IL-7R高表达MPECs不同,KLRG1高表达IL-7R低表达的SLECs依赖IL-15,但IL-15无法维持它们的长期维持或稳态更新。SLEC和MPEC命运之间的决定是由T细胞活化期间存在的炎性细胞因子(即IL-12)的量来调节的。根据炎症程度,形成了T-bet梯度,其中高T-bet表达诱导SLECs,低表达促进MPECs。这些结果阐明了一种机制,通过该机制先天性免疫系统设定了活化的CD8(+) T细胞中谱系决定转录因子的相对量,并相应地调节它们的记忆细胞潜能。
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