Ex vivo IL-15 replenishment augments bone marrow precursor cell-mediated adaptive immunity via PI3K-Akt pathway.

ABSTRACT

This study tested the hypothesis that PI3K-Akt activity contributes to the superior immune function of IL-15-administrated bone marrow precursor cells (BMPC). Our previous studies revealed that PI3K-Akt play vital role in dendritic cells (DCs) cross-presentation and DC-based CTL priming. Despite the fact that IL-15 serves multiple functions in its therapeutic potential for the induction and maintenance of T cell response, the exact role of PI3K-Akt in IL-15 increased adaptive immunity is still poorly understood. In this study, we demonstrated that ex vivo IL-15 administration increased BMPC capability of antigen uptake and the expression of costimulatory molecules (such as CD80 and 4-1BB(CD137) ligand [4-1BBL]) and MHC class I molecule via PI3K-Akt pathway. Importantly, PI3K-Akt activity was not only necessary for IL-15 augmented BMPC cross-presentation and CTL priming, but also facilitated IL-15 increased therapeutic potential of the cytolytic capacity and maintenance of BMPC-activated T cells. Thus, these data suggested that PI3K-Akt activity contribute to the superior immune function of IL-15-administrated BMPC and thereby might be therapeutic potential for adaptive immunity.