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 72 h) 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.

Keywords::

• Aspergillus fumigatus
• dendritic cells
• IL-12
• innate immunity
• lymphocytes

Acknowledgments

The author thanks Dr. Carolyn A. Keever-Taylor (Medical College of Wisconsin, Milwaukee, WI, USA) and Dr. Viswanath P. Kurup (VA Medical Center, Milwaukee, WI, USA) for technical support/discussion and kindly providing the Af-Cr antigen, respectively.

Declaration of interest

The author reports no declarations of interest.