TGF-β released by apoptotic T cells contributes to an immunosuppressive milieu
TGF-β released by apoptotic T cells contributes to an immunosuppressive milieu
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DOI：
10.1016/s1074-7613(01)00147-9
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发表时间：
2001-06-01
期刊：
影响因子：
32.4
通讯作者：
Wahl, SM
中科院分区：
文献类型：
--
作者：
Chen, WJ;Frank, ME;Wahl, SM
T细胞凋亡对免疫系统的发育和稳态至关重要。细胞凋亡最显著的特征是缺乏伴随的炎症反应或组织损伤。在这里，我们提出的证据表明，凋亡的T细胞释放TGF-β，从而有助于免疫抑制的环境。凋亡的T细胞不仅释放潜伏的，而且释放生物活性的TGF-β。尽管如此，TGF-β转录没有上调，这表明释放现有的而不是合成新的TGF-β。TGF-β定位于细胞内膜结合区室（包括线粒体）内，在线粒体膜电位丧失后重新分布到胞质溶胶中。由凋亡T细胞分泌的TGF-β抑制活化巨噬细胞产生促炎细胞因子以促进免疫抑制。这些发现拓宽了通过T细胞缺失诱导免疫耐受或免疫缺陷的潜在机制。
T cell apoptosis is critical to development and homeostasis of the immune system. The most salient feature of apoptosis is the lack of an attendant inflammatory response or tissue damage. Here, we present evidence that apoptotic T cells release TGF-beta, thereby contributing to an immunosuppressive milieu. Apoptotic T cells released not only latent but also bio-active TGF-beta. Nonetheless, TGF-beta transcription was not upregulated, suggesting release of existing rather than synthesis of new TGF-beta. Localized within the intracellular membrane-bound compartment, which includes mitochondria, TGF-beta was redistributed into the cytosol following loss of mitochondrial membrane potential. TGF-beta secreted from apoptotic T cells inhibited proinflammatory cytokine production by activated macrophages to foster immune suppression. These findings broaden the potential mechanisms whereby induction of immune tolerance or deficiency occurs through T cell deletion.