Previous studies showed that arginine-conjugated chitosan (ACS)/DNA nanoparticles (ACGN) mediated significantly higher expression of the transgenes when compared with chitosan (CS)/DNA nanoparticles (CGN). However, the interactions between ACGN and immune cells still remain poorly understood. The present study investigated whether ACGN affected the initial differentiation direction of human naive CD4(+) T cells, either directly or indirectly. It was demonstrated that both ACGN and CGN induced slightly higher production of IL-12 by THP-1 cells in the order of ACGN > CGN. However, this macrophage stimulating activity was much less significant when compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4(+) T cells separated from the nanoparticles and THP-1 cells by a 0.1-μm diameter polycarbonate semipermeable membrane, which allows the pass through of macromolecules including IL-12. It also demonstrated that, when directly exposed to naive CD4(+) T cells, none of the nanoparticles induced either the activation of the naive CD4(+) T cells in the absence of recombinant human IL-4 (rhIL-4) or IFN-γ (rhIFN-γ) that induce naive CD4(+) T cell polarization or any changes in the differentiation direction of the naive CD4(+) T cells in the presence of the corresponding cytokines.
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