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Author Notes:

E-mail address: rahmed@emory.edu; virgin@wustl.edu; karaki@emory.edu

X.X., K.A., S.L., M.W.B., J.M., D.R.G., D.P.J., H.W.V. and R.A. designed the research; X.X., K.A., S.L., J.-H.H., L.Y., W.G.T. and B.T.K. performed experiments.

X.X., K.A., S.L., M.W.B., E.L.P., D.R.G., D.P.J., H.W.V. and R.A. analyzed data; and X.X., K.A., S.L., E.L.P., H.W.V. and R.A. wrote the manuscript.

We thank A. Rao (La Jolla Institute for Allergy and Immunology) for the MSCV-IRES-Thy-1.1 retroviral vector; J. Jacob (Emory University) for Gzmb-Cre transgenic mice; V. Tran for the LC-MS experiments; R. Karaffa and S. Durham for sorting cells by flow cytometry at the Emory Flow Cytometry Core Facility; and A. Rae for assistance in the use of ImageStream.

The authors declare no competing financial interests.

Subjects:

Research Funding:

Supported by the US National Institutes of Health (R01 AI030048 to R.A. and R01 AI084887 to H.W.V.), the Mérieux Foundation (R.A.) and the Crohn's and Colitis Foundation (H.W.V.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • SELECTIVE AUTOPHAGY
  • EXPRESSION
  • PROTEIN
  • PERSISTENCE
  • ACTIVATION
  • MAINTAINS
  • IL-7

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

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Journal Title:

Nature Immunology

Volume:

Volume 15, Number 12

Publisher:

, Pages 1152-1161

Type of Work:

Article | Post-print: After Peer Review

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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