Opposing effects of TGF-beta and IL-15 cytokines control the number of short-lived effector CD8+ T cells.
Opposing effects of TGF-beta and IL-15 cytokines control the number of short-lived effector CD8+ T cells.
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DOI：
10.1016/j.immuni.2009.04.020
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发表时间：
2009-07-17
期刊：
影响因子：
32.4
通讯作者：
Flavell, Richard A.
中科院分区：
文献类型：
--
作者：
Sanjabi, Shomyseh;Mosaheb, Munir M.;Flavell, Richard A.
针对感染因子的有效免疫应答涉及CD 8 + T细胞的大量扩增。一旦感染被清除，这些效应细胞中的大多数通过未知的机制死亡，只留下记忆前体细胞。如何控制扩张以最大限度地清除病原体并最大限度地减少免疫病理学？我们发现，李斯特菌感染后，血浆TGF-β水平随着效应CD 8 + T细胞的扩增而增加。阻断TGF-β信号传导不影响CD 8 + T细胞的效应功能。然而，TGF-β通过降低Bcl-2水平和选择性地促进短寿命效应细胞的凋亡来控制效应细胞的数量。TGF-β介导的该效应子亚群的凋亡发生在克隆扩张和收缩期间，而IL-15仅在收缩期间促进其存活。我们证明了效应CD 8 + T细胞的数量在整个效应分化过程中受到多种外在信号的严格控制;这种可塑性应在疫苗设计和针对肿瘤和自身免疫性疾病的免疫治疗中加以利用。
An effective immune response against infectious agents involves massive expansion of CD8+ T cells. Once the infection is cleared, the majority of these effector cells die through unknown mechanisms, leaving behind only memory precursor cells. How is expansion controlled to maximize pathogen clearance and minimize immunopathology? We found, following Listeria infection, plasma TGF-β levels increased concomitant with the expansion of effector CD8+ T cells. Blocking TGF-β signaling did not affect effector function of CD8+ T cells. However, TGF-β controlled effector cell number by lowering Bcl-2 levels and selectively promoting the apoptosis of short-lived effector cells. TGF-β-mediated apoptosis of this effector sub-population occurred during clonal expansion and contraction, while IL-15 promoted their survival only during contraction. We demonstrate that the number of effector CD8+ T cells is tightly controlled by multiple extrinsic signals throughout effector differentiation; this plasticity should be exploited during vaccine design and immunotherapy against tumors and autoimmune diseases.
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影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
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影响因子：
158.5
作者：
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DOI：
10.1073/pnas.0705007104
发表时间：
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影响因子：
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作者：
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作者：
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