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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 38; pp. 16601 - 16606
• Main Authors: Hand, Timothy W., Cui, Weiguo, Jung, Yong Woo, Sefik, Esen, Joshi, Nikhil S., Chandele, Anmol, Liu, Ying, Kaech, Susan M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 21.09.2010; National Acad Sciences
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Apoptosis; Biological Sciences; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell growth; Cell lines; Cell Survival; Cytokines; Data processing; Down-Regulation; Effector cells; Gene expression regulation; Homeostasis; Immunologic Memory; Immunological memory; Infection; Infections; Interleukin 15; Interleukin 15 receptors; Interleukin 7; Interleukin-15 - pharmacology; Lymphocytes; Lymphocytes T; Lymphocytic choriomeningitis virus - immunology; Lymphocytic choriomeningitis virus - pathogenicity; Memory; Memory cells; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Receptors; Receptors, Cytokine - metabolism; Receptors, Immunologic - metabolism; Signal Transduction; Stat5 protein; STAT5 Transcription Factor - metabolism; T cell receptors; T lymphocytes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1003457107

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.