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
Date
09/09/2010Pubmed ID
20823247Pubmed Central ID
PMC2944719DOI
10.1073/pnas.1003457107Scopus ID
2-s2.0-78049268109 (requires institutional sign-in at Scopus site) 188 CitationsAbstract
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.
Author List
Hand TW, Cui W, Jung YW, Sefik E, Joshi NS, Chandele A, Liu Y, Kaech SMMESH terms used to index this publication - Major topics in bold
AnimalsCD8-Positive T-Lymphocytes
Cell Survival
Down-Regulation
Immunologic Memory
Interleukin-15
Lectins, C-Type
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
