: The use of chitosan nanoparticles as carriers for expression plasmids represents a major improvement in gene expression technology. We demonstrated previously that treatment with chitosan interferon-gamma (IFN-gamma) plasmid deoxyribonucleic acid (DNA) nanoparticles (chitosan interferon-gamma nanogene [CIN]) led to in situ production of IFN-gamma and a reduction in inflammation and airway reactivity in mice, but the mechanism underlying the immunomodulatory effects of CIN remains unclear. In this report, the effect of CIN treatment on the immune responses of CD8+ T cells and dendritic cells was examined in a BALB/c mouse model of ovalbumin (OVA)-induced allergic asthma. OT1 mice (OVA-T cell receptor [TCR] transgenic) were also used to test the effects of CIN on OVA-specific CD8+ T cells. CIN treatment caused a reduction in IFN-gamma production in a subpopulation of OVA-specific CD8+ T cells cultured in vitro in the presence of OVA. CIN also reduced apoptosis of the CD8+ T cells. Examination of dendritic cells from lung and lymph nodes indicated that CIN treatment decreased their antigen-presenting activity, as evident from the reduction in CD80 and CD86 expression. Furthermore, CIN treatment significantly decreased the number of CD11c+b+ dendritic cells in lymph nodes, suggesting that endogenous IFN-gamma expression may immunomodulate dendritic cell migration and activation. CIN therapy results in a reduction in proinflammatory CD8+ T cells and decreases the number and antigen-presenting activity of dendritic cells.