Institut Pasteur, Dynamics of Immune Responses Unit, 75015 Paris, France; INSERM U668, 75015 Paris, France.
Cell Rep. 2012 Nov 29;2(5):1438-47. doi: 10.1016/j.celrep.2012.10.015. Epub 2012 Nov 15.
Contraction is a critical phase of immunity whereby the vast majority of effector T cells die by apoptosis, sparing a population of long-lived memory cells. Where, when, and why contraction occurs has been difficult to address directly due in large part to the rapid clearance of apoptotic T cells in vivo. To circumvent this issue, we introduced a genetically encoded reporter for caspase-3 activity into naive T cells to identify cells entering the contraction phase. Using two-photon imaging, we found that caspase-3 activity in T cells was maximal at the peak of the response and was associated with loss of motility followed minutes later by cell death. We demonstrated that contraction is a widespread process occurring uniformly in all organs tested and targeting phenotypically diverse T cells. Importantly, we identified a critical window of time during which antigen encounters act to antagonize T cell apoptosis, supporting a causal link between antigen clearance and T cell contraction. Our results offer insight into a poorly explored phase of immunity and provide a versatile methodology to study apoptosis during the development or function of a variety of immune cells in vivo.
收缩是免疫的一个关键阶段，在此期间，绝大多数效应 T 细胞通过细胞凋亡死亡，留下一群长寿的记忆细胞。由于体内凋亡 T 细胞的快速清除，收缩发生的时间、地点和原因一直难以直接解决。为了解决这个问题，我们将一种用于 caspase-3 活性的基因编码报告基因引入到幼稚 T 细胞中，以鉴定进入收缩阶段的细胞。通过双光子成像，我们发现 T 细胞中的 caspase-3 活性在反应高峰期达到最大值，与运动性丧失相关，几分钟后随后发生细胞死亡。我们证明收缩是一个广泛发生的过程，发生在所有测试的器官中，针对表型多样的 T 细胞。重要的是，我们确定了一个关键的时间窗口，在此期间，抗原的出现会拮抗 T 细胞凋亡，支持抗原清除和 T 细胞收缩之间的因果关系。我们的结果为免疫的一个研究甚少的阶段提供了深入的了解，并提供了一种通用的方法来研究体内各种免疫细胞在发育或功能过程中的细胞凋亡。
