Influence of autologous dendritic cells on the in-vitro expansion and functions of peripheral blood NK cells

Abstract

Context: Allogeneic reactive NK cells were previously shown to exert a graft-versus-leukemia (GVL) effect during allogeneic hematopoietic stem cell transplantation, as well as reduce the incidence of graft-versus-host disease (GVHD).

Objective: We used autologous immature DCs as feeder cells for the in-vitro expansion of NK cells and studied the function of the NK cell cultures.

Materials and methods: NK cells were cultured for 15 days in the presence of autologous, immature DCs. Fold expansion, killing activity and expression of IFN-γ, perforin and granzyme B were evaluated.

Results: The highest NK cell expansion efficiency was observed when the ratio of NK cells:DCs was 2:1 and when cells were cultured in a contact-dependent manner. The killing activity of NK cells was highest when the NK:DC ratio was 10:1. NK cell cultures exhibited a significant upregulation in the mRNA expression of IFN-γ, perforin and granzyme B when the ratio of NK cells to DCs was 10:1.

Discussion: We successfully amplified NK cells using autologous immature DCs derived from human peripheral monocytes after induction as feeder cells. The use of autologous immature DCs for ex-vivo expansion of NK cells can be clinically applied to overcome limitations, such as the small number of NK cells in peripheral blood, and the high cost of NK cell sorting. Transfusion of allogeneic reactive NK cells has been suggested as a potential adjunctive therapeutic strategy after transplantation.

Conclusion: Autologous immature DCs can be used as feeder cells for ex-vivo expansion of functional NK cells.

• Dendritic cells
• feeder cells
• immune response
• natural killer cells
• proliferation

Supplementary material available online

Supplementary Tables 1 and 2.