Autophagy is essential for effector CD8+ T cell survival and memory formation

X Xu, K Araki, S Li, JH Han, L Ye, WG Tan… - Nature …, 2014 - nature.com
X Xu, K Araki, S Li, JH Han, L Ye, WG Tan, BT Konieczny, MW Bruinsma, J Martinez…
Nature immunology, 2014nature.com
The importance of autophagy in the generation of memory CD8+ T cells in vivo is not well
defined. We report here that autophagy was dynamically regulated in virus-specific CD8+ T
cells during acute infection of mice with lymphocytic choriomeningitis virus. In contrast to the
current paradigm, autophagy decreased in activated proliferating effector CD8+ T cells and
was then upregulated when the cells stopped dividing just before the contraction phase.
Consistent with those findings, deletion of the gene encoding either of the autophagy-related …
Abstract
The importance of autophagy in the generation of memory CD8+ T cells in vivo is not well defined. We report here that autophagy was dynamically regulated in virus-specific CD8+ T cells during acute infection of mice with lymphocytic choriomeningitis virus. In contrast to the current paradigm, autophagy decreased in activated proliferating effector CD8+ T cells and was then upregulated when the cells stopped dividing just before the contraction phase. Consistent with those findings, deletion of the gene encoding either of the autophagy-related molecules Atg5 or Atg7 had little to no effect on the proliferation and function of effector cells, but these autophagy-deficient effector cells had survival defects that resulted in compromised formation of memory T cells. Our studies define when autophagy is needed during effector and memory differentiation and warrant reexamination of the relationship between T cell activation and autophagy.
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