Vγ9γδ T Cell Induction by Human Umbilical Cord Blood Monocytes-Derived, Interferon-α-Stimulated Dendritic Cells

Abstract

Dendritic cells (DC) are professional antigen-presenting cells that activate T cells to kill cancer cells. The extracellular products of DCs have also been reported to perform the same function. In this study, we examined the in vitro differentiation of umbilical cord blood monocytes into DCs in the presence of GM-CSF, and interferon (IFN)-α. The resulting DC population (called IFN-DCs) were then matured in the presence of TNF-α, and pulsed with total protein extracted from A549 cancer cell line. The pulsed DCs and their conditioned medium were then used to stimulate allogeneic lymphocytes (alloLym). The proliferation and cytotoxicity of alloLym were then determined. The results showed that after 5 days of differentiation, the stimulated monocytes had the typical morphology and characteristic surface markers of DCs. Both unpulsed and pulsed IFN-DCs can induce the proliferation of alloLym, especially Vγ9γδ T cells. The conditioned medium from pulsed and unpulsed IFN-DCs culture also prompted the growth of Vγ9γδ T cells. Moreover, alloLym stimulated with pulsed DCs and their conditioned medium had a greater cytotoxic effect on A549 cells than the ones that were not stimulated. Our results indicated that IFN-DCs and their conditioned medium could induce the anti-tumor immunity in vitro, providing evidence for application of cord blood monocytes-derived, interferon-α- stimulated dendritic cells and their extracellular products in anti-cancer therapy.

Cord-Blood-Derived Professional Antigen-Presenting Cells: Functions and Applications in Current and Prospective Cell Therapies

“…Various ligands, including the TLR2, TLR3, TLR4, and TLR8 ligands, are able to induce equal or higher amounts of IL-23 from UCB-derived MoDC, which is critical for the proliferation of T H 17 T cells [ 33 , 70 , 71 ]. Additional reports unveiled that UCB-derived MoDC are able to induce Vγ9γδ T cell proliferation and cytotoxic behavior following generation with IFNα and GM-CSF [ 72 ]. Considering these observations, UCB-derived MoDC are generally thought to exhibit tolerogenic characteristics mediating the suppression of allograft rejection and supporting the survival of the fetus.…”

“…In an in vitro model, Anh and colleagues studied the effects of IFNα-induced UCB-MoDC on allogenic adult T cells [ 72 ]. Here, IFNα-induced UCB-MoDC induced a 46.1 + 9.3-fold increase in Vγ9γδ T cells with CD4 + and CD8 + T cell numbers declining after 7 days of co-culture, similarly to conditioned media from IFNα-induced UCB-MoDC.…”

“…Here, IFNα-induced UCB-MoDC induced a 46.1 + 9.3-fold increase in Vγ9γδ T cells with CD4 + and CD8 + T cell numbers declining after 7 days of co-culture, similarly to conditioned media from IFNα-induced UCB-MoDC. In addition, IFNα-induced UCB-MoDC enhanced the cytotoxic capabilities of allogenic Vγ9γδ T cells in terms of A549 tumor cell lysis [ 72 ]. Previous studies were able to show that Vγ9γδ T cells halted tumor growth in vivo and in vitro by reducing the activation of pro-survival molecules and increasing the levels of apoptotic molecules, including the AKT and ERK signaling pathways [ 170 ].…”