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Introduction
IL-15 is a potent growth and mobilization factor for many lymphocytes, including NK, CD8+ and intraepithelial lymphocytes [1-3] . The bioactive IL-15 cytokine consists of 2 chains in vivo, IL-15 in complex with the so-called IL-15 Receptor alpha (IL-15R[alpha]), which together form the cytokine found in both human and mouse plasma [4] . We have previously reported that co-expression of IL-15 and IL-15R[alpha] within the same cell leads to rapid intracellular association of the two chains in the endoplasmic reticulum, resulting in the stabilization and export of both molecules to the cell surface, where the complex is rapidly cleaved and released as a functional extracellular cytokine [5] . IL-15 knock-out (KO) mice are characterized by the almost complete absence of NK cells and the severe reduction of CD8+ T lymphocytes, especially those with memory phenotype (CD44hi ), which suggests a role for IL-15 in the maintenance of memory CD8+ T cells [3] . In fact, several studies have reported a role of IL-15 in promoting the homeostatic proliferation and survival of long-term memory CD8+ T cells [6-11] . It has also been demonstrated that IL-15 promotes the survival of effector CD8+ T cells through the induction of the anti-apoptotic molecules Bcl-2 and Bcl-xL, preserving a subset of CD8+ T cells during the contraction of primary immune responses, and subsequently promoting their transition into long-term memory CD8+ T cells [12-18] .
In addition to its role on the survival of memory CD8+ T cells, it has been reported that IL-15 plays an important role in the generation of primary antigen-specific CD4+ and CD8+ T cell responses [6,19-21] . In contrast, other studies indicated that IL-15 is dispensable for the generation of T cell responses [7-9,13,22-26] , concluding that IL-15 is required only for the long-term maintenance of the antigen-specific memory CD8+ T cell pool [7-10] . Moreover, a large body of evidence indicates that IL-15 plays important roles in the induction of cytotoxic CD8+ T cells [27-31] . However, other works revealed IL-15-independent generation and maintenance of functional memory CD8+ T cells against several infectious agents [24,32,33] . Conflicting data have also been reported regarding the role of IL-15 in...