Pua Heather H, He You-Wen
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Autophagy. 2007 May-Jun;3(3):266-7. doi: 10.4161/auto.3908. Epub 2007 May 24.
First identified as a pathway for nutrient recovery during periods of starvation, the role of autophagy has expanded to the clearance of "toxic" intracellular material including ubiquitin-positive protein aggregates, damaged organelles as well as microbial pathogens in various cell types. We have examined the role of autophagy in the development and function of the adaptive immune system. Genes encoding autophagy machinery are expressed in T lymphocytes, and autophagy occurs in primary CD4+ and CD8+ T cells. By generating fetal liver chimeric mice, we found that thymocyte development is largely normal but the mature T cell compartment is severely reduced in the absence of the essential autophagy gene Atg5. Consistent with a critical role for autophagy in promoting T cell survival, Atg5-/- CD8+ T cells display high levels of apoptosis. Surprisingly, Atg5-deficient T cells were also unable to efficiently proliferate after T-cell receptor (TCR) stimulation. These findings suggest that autophagy regulates T lymphocyte homeostasis by promoting both survival and proliferation. In addition, T cells offer a new, physiologically relevant system to study the regulation and function of autophagy pathways in vivo.
自噬最初被认为是饥饿期间营养物质回收的一条途径，其作用已扩展到清除“有毒”的细胞内物质，包括泛素阳性蛋白聚集体、受损细胞器以及各种细胞类型中的微生物病原体。我们研究了自噬在适应性免疫系统发育和功能中的作用。编码自噬机制的基因在T淋巴细胞中表达，自噬发生在原代CD4+和CD8+T细胞中。通过构建胎肝嵌合小鼠，我们发现胸腺细胞发育基本正常，但在缺乏必需的自噬基因Atg5的情况下，成熟T细胞区室严重减少。与自噬在促进T细胞存活中的关键作用一致，Atg5-/-CD8+T细胞表现出高水平的凋亡。令人惊讶的是，Atg5缺陷型T细胞在T细胞受体（TCR）刺激后也无法有效增殖。这些发现表明，自噬通过促进存活和增殖来调节T淋巴细胞的稳态。此外，T细胞为体内研究自噬途径的调节和功能提供了一个新的、生理相关的系统。
