Puleston D J, Simon A K
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS.
Microb Cell. 2015 Mar 2;2(3):91-93. doi: 10.15698/mic2015.03.195.
The conserved lysosomal degradation pathway autophagy is now recognised as an essential cog in immune function. While functionally widespread in the innate immune system, knowledge of its roles in adaptive immunity is more limited. Although autophagy has been implicated in naïve T cell homeostasis, its requirement in antigen-specific T cells during infection was unknown. Using a murine model where the essential autophagy gene is deleted in the T cell lineage, we have shown that autophagy is dispensable for effector CD8 T cell responses, but crucial for the formation of memory CD8 T cells. Here, we suggest reasons why autophagy might be important for the formation of long-lasting immunity. Like in the absence of autophagy, T cell memory formation during ageing is also defective. We observed diminished autophagy levels in T cells from aged mice, linking autophagy to immunosenescence. Importantly, T cell responses to influenza vaccination could be significantly improved using the autophagy-inducing compound spermidine. These results suggest the autophagy pathway as a desirable target to improve aged immunity and modulate T cell function.
保守的溶酶体降解途径自噬现在被认为是免疫功能中一个重要的组成部分。虽然自噬在固有免疫系统中功能广泛，但对其在适应性免疫中作用的了解却较为有限。尽管自噬与初始T细胞的稳态有关，但其在感染期间对抗抗原特异性T细胞的需求尚不清楚。通过使用一种在T细胞谱系中缺失关键自噬基因的小鼠模型，我们发现自噬对于效应CD8 T细胞反应是可有可无的，但对于记忆CD8 T细胞的形成至关重要。在这里，我们提出了自噬可能对持久免疫形成很重要的原因。就像在没有自噬的情况下一样，衰老过程中T细胞记忆形成也存在缺陷。我们观察到老年小鼠T细胞中的自噬水平降低，这将自噬与免疫衰老联系起来。重要的是，使用自噬诱导化合物亚精胺可以显著改善T细胞对流感疫苗接种的反应。这些结果表明自噬途径是改善老年免疫和调节T细胞功能的理想靶点。
