Autophagy Is Essential for Effector CD8(+) T Cell Survival and Memory Formation

Nat Immunol. 2014 Dec;15(12):1152-61. doi: 10.1038/ni.3025. Epub 2014 Nov 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Cell Separation
  • Cell Survival / immunology
  • Chromatography, Liquid
  • Flow Cytometry
  • Immunoblotting
  • Immunologic Memory / immunology*
  • Lymphocyte Activation / immunology
  • Lymphocytic Choriomeningitis / immunology
  • Mass Spectrometry
  • Mice
  • Mice, Mutant Strains
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Transduction, Genetic

Associated data

  • GEO/GSE57047