In vitro expansion of human γδ and CD56⁺T-cells by Aspergillus-antigen loaded fast dendritic cells in the presence of exogenous interleukin-12

Abstract

Aspergillus fumigatus (Af) infection is especially prevalent after allogenic bone marrow transplantation (BMT) and causes invasive pulmonary aspergillosis. Human γδ T-cells have essential role in maintaining immune homeostasis and in the resistance of pathogens and tumors. Also, γδ T-cells may facilitate stem cells engraftment and decrease a life-threatening graft versus host disease after allogenic BMT. Moreover, expression of CD56 molecules on γδ T-cells increases their antitumor cytotoxic activity. This study reveals that Af-pulsed fast dendritic cells (fast-DCs, which generated within only 72h) plus IL-12 and then IL-2 can propagate autologous γδ and CD56 + T-cells in vitro and this expansion is sustained by repeating the stimulation (107.5±13.9-fold and 37.6±2.2-fold increase for γδ and CD56 + T-cells, respectively, after three primings). Many of the expanded γδ and CD56 + T-cells expressed CD8 molecules (29.6%-68.6%), while few of them expressed CD4 molecules (2.3%-17.5%). Also, ∼28% of the expanded γδ T-cells were CD56 + . On the other hand, the proliferation of γδ and CD56 + T-cells significantly decreased (p < 0.001, < 19-fold and 12-fold, respectively) in the absence of either Af-pulsed fast-DCs or IL-12 or in the presence of un-pulsed fast-DCs, indicating the importance of Af-antigens and IL-12 in inducing this expansion. The expansion of γδ and CD56 + T-cells did not hamper the generation of Af-specific αβ T-cell effectors. The methodology described in this study, utilizing autologous Af-pulsed fast-DCs and IL-12, permits the rapid generation of Af-specific αβ T-cell effectors and propagation of γδ and CD56 + T-cells in vitro. © 2012 Informa Healthcare USA, Inc.