In vivo overexpression of Flt3 ligand expands and activates murine spleen natural killer dendritic cells. Academic Article uri icon

Overview

abstract

  • Natural killer dendritic cells (NKDC) are a unique class of murine immune cells that possess the characteristics of both natural killer (NK) cells and dendritic cells (DC). Because NKDC are able to secrete IFN-gamma, directly lyse tumor cells, and present antigen to naïve T cells, they have immunotherapeutic potential. The relative paucity of NKDC, however, impedes their detailed study. We have found that in vivo, overexpression of the hematopoietic cytokine Flt3 ligand (Flt3L) expands NKDC in various organs from 2-18 fold. Flt3L expanded splenic NKDC retain the ability to lyse tumor cells and become considerably more potent at activating naïve allogeneic and antigen-specific T cells. Compared to normal splenic NKDC, Flt3L-expanded splenic NKDC have a more mature phenotype, a slightly increased ability to capture and process antigen, and a similar cytokine profile. In vivo, we found that Flt3L-expanded splenic NKDC are more effective than normal splenic NKDC in stimulating antigen-specific CD8 T cells. Additionally, we show that NKDC are able to cross-present antigen in vivo. The ability to expand NKDC in vivo using Flt3L will facilitate further analysis of their unique biology. Moreover, Flt3L-expanded NKDC may have enhanced immunotherapeutic potential, given their increased ability to stimulate T cells.

publication date

  • March 29, 2006

Research

keywords

  • Dendritic Cells
  • Killer Cells, Natural
  • Lymphocyte Activation
  • Membrane Proteins
  • Spleen

Identity

Scopus Document Identifier

  • 33845669440

Digital Object Identifier (DOI)

  • 10.1096/fj.05-5411fje

PubMed ID

  • 16571772

Additional Document Info

volume

  • 20

issue

  • 7