Expansion of Foxp3-expressing regulatory T cells in vitro by dendritic cells modified with polymeric particles carrying a plasmid encoding interleukin-10.

Abstract

An emerging focus in experimental gene therapy is to employ non-viral vectors to deliver immunosuppressive cytokines aimed at attenuating damaging immune responses toward auto and alloantigens. In the current study, we present data showing that poly(lactic-co-glycolic acid) (PLGA) particles modified with the cationic peptide O10H6 (PLGA(O10H6)) were effective in delivering a mouse IL-10 encoding plasmid (pIL10) to skew bone marrow-derived dendritic cells (DCs) to downregulate T cell responses. T cells stimulated by the IL-10 gene-modified DCs exhibited characteristics of regulatory T (Treg) cells, as evident by upregulation of Foxp3 transcription factor concomitant with an increase in TGFbeta production. Thus PLGA(O10H6) complexed with pIL10 delivers an overriding suppressive signal to T cells. Physical characterization of PLGA(O10H6) complexed with pIL10 revealed a stable colloidal dispersion. DNA molecules carried by PLGA(O10H6) were protected from serum digestion. Collectively, the results raise the prospects of using PLGA(O10H6) as a vector for delivering anti-inflammatory cytokine genes to modulate T cell responses in vivo.