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

作者：Hand Timothy W; Cui Weiguo; Jung Yong Woo; Sefik Esen; Joshi Nikhil S; Chandele Anmol; Liu Ying; Kaech Susan M^*

来源：Proceedings of the National Academy of Sciences, 2010, 107(38): 16601-16606.

DOI：10.1073/pnas.1003457107

• apoptosis
• cytokine signaling
• interleukin 15
• interleukin 7
• lymphocytic choriomeningitis virus

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.

• 出版日期2010-9-21