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

Timothy W Hand, Weiguo Cui, Yong Woo Jung, Esen Sefik, Nikhil S Joshi, Anmol Chandele, Ying Liu, Susan M Kaech

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)16601-6
Number of pages6
JournalProceedings of the National Academy of Sciences (PNAS)
Issue number38
Publication statusPublished - 21 Sept 2010

Keywords / Materials (for Non-textual outputs)

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


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