title: IL-15 activates telomerase and minimizes telomere loss and may preserve the replicative life span of memory CD8+ T cells in vitro.
abstract: The preservation of the replicative life span of memory CD8(+) T cells is vital for long-term immune protection. Although IL-15 plays a key role in the homeostasis of memory CD8(+) T cells, it is unknown whether IL-15 regulates the replicative life span of memory CD8(+) T cells. In this study, we report an analysis of telomerase expression and telomere length in human memory phenotype CD8(+) T cells maintained by IL-15 in vitro. We demonstrate that IL-15 is capable of activating telomerase in memory CD8(+) T cells via Jak3 and PI3K signaling pathways. Furthermore, IL-15 induces a sustained level of telomerase activity over long periods of time, and in turn minimizes telomere loss in memory CD8(+) T cells after substantial cell divisions. These findings suggest that IL-15 activates stable telomerase expression and compensates telomere loss in memory phenotype CD8(+) T cells, and that telomerase may play an important role in memory CD8(+) T cell homeostasis.
authors.affiliation: Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Wang
authors.initials: W
authors.lastname: Zhi
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Wareski
authors.forename: Nan-ping
authors.initials: NP
authors.lastname: Weng
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000502:physiology*; D016922:Cellular Senescence / Q000276:immunology*; D004789:Enzyme Activation; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000502:physiology*; D053616:Janus Kinase 3; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D019409:Interleukin-15; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D019098:Telomerase