The dynamic impact of hydrodynamic gene transfer on the immune system

Hydrodynamic gene transfer (HGT) has been used as an effective and convenient way to achieve gene expressions in vivo. However, its time-dependent impact on the immune system is unknown. The aim of the current study is to investigate the dynamic changes of the immune parameters after HGT. Plasmids were delivered to BALB/c mice by HGT. Each group of mice was sacrificed on day 1, 2, 3, 4 and 5 after HGT. The immune cell subsets from spleens and livers were analyzed by flow cytometry. IFN-γ, IL-6 and TNF-α in the serum were quantitated by cytometric bead array. The mice without HGT injection were used as control group on day 0. Compared to the normal mice (day 0), the T lymphocyte infiltrations in the spleen and liver were increased starting from day 1 after HGT. T cells. NK cells and myeloid cells such as dendritic cells, neutrophils and macrophages were also significantly expanded and peaked around day 2-3. Both T cells and NK cells were greatly activated. Serum levels of IFN-γ and IL-6 increased and peaked on day 1 after HGT. Most of the increased immune parameters returned to normal levels after day 4. However, the activated T cells remained at a high level, especially in the liver. In conclusion, HGT significantly increased the immune cell infiltration in the spleen and liver and activated T cells and NK cells. The immune response induced by HGT should be taken into consideration when evaluating the functions of the over-expressed genes using this strategy.