Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival.
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.
Hand
Timothy W
TW
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Cui
Weiguo
W
Jung
Yong Woo
YW
Sefik
Esen
E
Joshi
Nikhil S
NS
Chandele
Anmol
A
Liu
Ying
Y
Kaech
Susan M
SM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002470:Cell Survival; D015536:Down-Regulation; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000494:pharmacology; D037181:Lectins, C-Type; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
D019409:Interleukin-15; D037181:Lectins, C-Type; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D050799:STAT5 Transcription Factor; C451496:Klrg1 protein, mouse
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