Pua Heather H, Dzhagalov Ivan, Chuck Mariana, Mizushima Noboru, He You-Wen
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Exp Med. 2007 Jan 22;204(1):25-31. doi: 10.1084/jem.20061303. Epub 2006 Dec 26.
Macroautophagy (hereafter referred to as autophagy) is a well-conserved intracellular degradation process. Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential roles in cell survival during starvation, in innate cell clearance of microbial pathogens, and in neural cell maintenance. However, the role of autophagy in T lymphocyte development and survival is not known. Here, we demonstrate that autophagosomes form in primary mouse T lymphocytes. By generating Atg5-/- chimeric mice, we found that Atg5-deficient T lymphocytes underwent full maturation. However, the numbers of total thymocytes and peripheral T and B lymphocytes were reduced in Atg5 chimeras. In the periphery, Atg5-/- CD8+ T lymphocytes displayed dramatically increased cell death. Furthermore, Atg5-/- CD4+ and CD8+ T cells failed to undergo efficient proliferation after TCR stimulation. These results demonstrate a critical role for Atg5 in multiple aspects of lymphocyte development and function and suggest that autophagy may be essential for both T lymphocyte survival and proliferation.
巨自噬（以下简称自噬）是一种高度保守的细胞内降解过程。最近对缺乏自噬基因Atg5和Atg7的细胞进行的研究表明，自噬在饥饿期间的细胞存活、微生物病原体的天然细胞清除以及神经细胞维持中起着至关重要的作用。然而，自噬在T淋巴细胞发育和存活中的作用尚不清楚。在此，我们证明在原代小鼠T淋巴细胞中形成了自噬体。通过生成Atg5基因敲除嵌合小鼠，我们发现Atg5缺陷的T淋巴细胞能够完全成熟。然而，Atg5嵌合体中总胸腺细胞以及外周T和B淋巴细胞的数量减少。在外周，Atg5基因敲除的CD8⁺ T淋巴细胞表现出显著增加的细胞死亡。此外，Atg5基因敲除的CD4⁺和CD8⁺ T细胞在TCR刺激后未能进行有效的增殖。这些结果证明了Atg5在淋巴细胞发育和功能的多个方面起着关键作用，并表明自噬可能对T淋巴细胞的存活和增殖都至关重要。
