Attenuated alloreactivity of dendritic cells engineered with surface-modified microspheres carrying a plasmid encoding interleukin-10.
In the present study, we investigated MS(O10H6) as a carrier system to introduce a plasmid encoding murine interleukin-10 (pIL-10) to modulate alloreactivity of dendritic cells (DC). Results indicate that MS(O10H6) formed stable and protective nano-sized particles with pIL-10. Gene-modified DC elicited weak proliferation of allogeneic CD4 and CD8 T cells in vitro. Using cell-embedded Matrigel as a surrogate graft, we also showed that DC transfected with MS(O10H6) complexed with pIL-10 suppressed host cell infiltration in vivo. These data demonstrate that the self-assembled system of MS(O10H6) is an effectual delivery vehicle for plasmid-based modulation of DC-dependent allogeneic T cell responses.
Jia
Liang
L
Division of Pharmaceutical Sciences, Duquesne University, 600 Forbes Ave., Mellon 413, Pittsburgh, PA, USA.
Kovacs
Jeffrey R
JR
Zheng
Ying
Y
Gawalt
Ellen S
ES
Shen
Hongmei
H
Meng
Wilson S
WS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D018014:Gene Transfer Techniques; D006639:Histidine / Q000737:chemistry*; D016753:Interleukin-10 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009952:Ornithine / Q000737:chemistry*; D010957:Plasmids / Q000235:genetics
D016753:Interleukin-10; D006639:Histidine; D009952:Ornithine