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

J Leukoc Biol. 2020 Jul;108(1):177-188. doi: 10.1002/JLB.1MA0220-337RR. Epub 2020 Apr 15.

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.

Keywords: Akt; PI3K; bone marrow precursor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects*
  • Animals
  • Antigens / metabolism
  • Bone Marrow Cells / immunology*
  • Cross-Priming / drug effects
  • Cytosol / metabolism
  • Female
  • Immunologic Memory / drug effects
  • Interleukin-15 / pharmacology*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens
  • Interleukin-15
  • Proto-Oncogene Proteins c-akt