Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival

Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16601-6. doi: 10.1073/pnas.1003457107. Epub 2010 Sep 7.


During viral infection, effector CD8 T cells contract to form a population of protective memory cells that is maintained by IL-7 and IL-15. The mechanisms that control effector cell death during infection are poorly understood. We investigated how short- and long-lived antiviral CD8 T cells differentially used the survival and cell growth pathways PI3K/AKT and JAK/STAT5. In response to IL-15, long-lived memory precursor cells activated AKT significantly better than short-lived effector cells. However, constitutive AKT activation did not enhance memory CD8 T-cell survival but rather repressed IL-7 and IL-15 receptor expression, STAT5 phosphorylation, and BCL2 expression. Conversely, constitutive STAT5 activation profoundly enhanced effector and memory CD8 T-cell survival and augmented homeostatic proliferation, AKT activation, and BCL2 expression. Taken together, these data illustrate that effector and memory cell viability depends on properly balanced PI3K/AKT signaling and the maintenance of STAT5 signaling.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Survival
  • Down-Regulation
  • Immunologic Memory
  • Interleukin-15 / pharmacology
  • Lectins, C-Type
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptors, Cytokine / metabolism
  • Receptors, Immunologic / metabolism
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction


  • Interleukin-15
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Cytokine
  • Receptors, Immunologic
  • STAT5 Transcription Factor
  • Proto-Oncogene Proteins c-akt