Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells.

Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells.
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DOI:
10.1084/jem.20020033
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发表时间:
2002-06-17
影响因子:
15.3
通讯作者:
Butz, Eric A
Butz, Eric A
中科院分区:
医学1区
文献类型:
--
作者:
Goldrath, Ananda W;Sivakumar, Pallavur V;Glaccum, Moira;Kennedy, Mary K;Bevan, Michael J;Benoist, Christophe;Mathis, Diane;Butz, Eric A

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初始T细胞和记忆T细胞在转移到T细胞枯竭的环境(急性稳态增殖)后都经历抗原不依赖的增殖,而只有记忆T细胞在一个完整的T细胞室中缓慢分裂(基底增殖)。我们发现,首先,幼稚和记忆CD8+ T细胞对急性稳态增殖有不同的细胞因子需求。白细胞介素(IL)-7受体(R)α介导的信号是淋巴细胞减少宿主中幼稚T细胞增殖的必需信号,而IL-15不影响其分裂。另一方面,记忆T细胞可以使用IL-7Rα -或IL-15介导的信号进行急性稳态增殖:当IL-7Rα被阻断或IL-15被去除时,它们的增殖被延迟,但只有当这两种信号缺失时,增殖才会消失。其次,CD8+记忆T细胞的基础和急性稳态增殖所需的细胞因子不同,因为在il -15缺陷的宿主中,记忆T细胞的基础分裂被完全阻断。这些数据提示IL-15 -和il - 15r α -缺陷小鼠记忆性CD8+ T细胞缺乏的可能机制是它们的基础增殖受损。我们的研究结果表明,幼稚T淋巴细胞和记忆T淋巴细胞对急性稳态增殖的细胞因子依赖性不同,记忆T淋巴细胞在满室和空室中增殖有不同的要求。
Both naive and memory T cells undergo antigen-independent proliferation after transfer into a T cell–depleted environment (acute homeostatic proliferation), whereas only memory T cells slowly divide in a full T cell compartment (basal proliferation). We show, first, that naive and memory CD8+ T cells have different cytokine requirements for acute homeostatic proliferation. Interleukin (IL)-7 receptor(R)α–mediated signals were obligatory for proliferation of naive T cells in lymphopenic hosts, whereas IL-15 did not influence their division. Memory T cells, on the other hand, could use either IL-7Rα– or IL-15–mediated signals for acute homeostatic proliferation: their proliferation was delayed when either IL-7Rα was blocked or IL-15 removed, but only when both signals were absent was proliferation ablated. Second, the cytokine requirements for basal and acute homeostatic proliferation of CD8+ memory T cells differ, as basal division of memory T cells was blocked completely in IL-15–deficient hosts. These data suggest a possible mechanism for the dearth of memory CD8+ T cells in IL-15– and IL-15Rα–deficient mice is their impaired basal proliferation. Our results show that naive and memory T lymphocytes differ in their cytokine dependence for acute homeostatic proliferation and that memory T lymphocytes have distinct requirements for proliferation in full versus empty compartments.