Role of Telomere And Telomerase In Human Lymphocyte Func

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Abstract

One of the key outstanding issues of immunological memory is how memory cells can survive and maintain their replicative capacity over long period of time in vivo. Recent studies indicate that homeostatic cytokines such as IL-7 and IL-15 play essential role in survival and maintenance of memory T cells. IL-7 appears important for the survival of both CD4+ and CD8+ memory T cells while IL-15 is capable of promoting proliferation and long-term survival of memory CD8+ T cells. While IL-15 plays a key role in the homeostasis of memory CD8+ T cells, it is unknown whether IL-15 regulates the replicative lifespan of memory CD8+ T cells. We have demonstrated that IL-15 is capable of inducing telomerase activity through activation of Jak3 and PI3-K/AKT signaling pathways in memory phenotype CD8+ T cells. Furthermore, IL-15 induced telomerase activity is associated with the relative stable telomere length in long term cultured memory phenotype CD8+ T cells. We also demonstrate that IL-7 induces higher levels of telomerase activity in naive CD4+ T cells than in memory CD4+ T cells despite of a better proliferative response of memory cells than naive cells under IL-7. As increase telomerase activity via enhanced expression the telomerase catalytic unit (hTERT) prevents telomere loss and extends their replicative lifespan of CD8+ and CD4+ T cells, homeostatic cytokines induced activation of telomerase can preserve telomere length in dividing memory T cells and preserve their replicative lifespan.