Functional modification of dendritic cells with recombinant adenovirus encoding interleukin 10 for the treatment of sepsis

• Published in: Shock (Augusta, Ga.) Vol. 23; no. 6; p. 507
• Main Authors: Oberholzer, Andreas, Oberholzer, Caroline, Efron, Philip A, Scumpia, Philip O, Uchida, Takefumi, Bahjat, Keith, Ungaro, Ricardo, Tannahill, Cynthia L, Murday, Michelle, Bahjat, Frances R, Tsai, Van, Hutchins, Beth, Moldawer, Lyle L, Laface, Drake, Clare-Salzler, Michael J
• Format: Journal Article
• Language: English
• Published: United States 01.06.2005
• Subjects: Adenoviridae - genetics; Adenoviridae - metabolism; Animals; Antigens, CD - biosynthesis; B7-2 Antigen; CD3 Complex - biosynthesis; CD40 Antigens - biosynthesis; Cell Survival; Cells, Cultured; Coculture Techniques; Dendritic Cells - cytology; Dendritic Cells - metabolism; Endocytosis; Female; Flow Cytometry; Genetic Therapy - methods; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Green Fluorescent Proteins - metabolism; Interleukin-10 - genetics; Interleukin-10 - therapeutic use; Interleukin-12 - metabolism; Lipopolysaccharides - metabolism; Lymph Nodes - pathology; Lymphocytes - cytology; Membrane Glycoproteins - biosynthesis; Mice; Mice, Inbred C57BL; Phenotype; Sepsis - metabolism; Sepsis - therapy; T-Lymphocytes - cytology; Th1 Cells; Th2 Cells - metabolism; Time Factors
• ISSN: 1073-2322
• DOI: 10.1097/01.shk.0000163208.29655.74

Control of dendritic cell (DC) function is critical for strategies to modulate innate and acquired immune responses. We examined whether transduction of murine DCs with adenoviral vectors (Adv) expressing interleukin (IL)-10 could alter their phenotype and T cell stimulatory function. Murine bone marrow-derived DCs were transduced with AdV encoding human IL-10 or green fluorescent protein (GFP). Whereas transduction of immature DCs with AdV/GFP resulted in dose-dependent maturation, DCs transduced with Adv/IL-10 maintained an immature state with low major histocompatibility complex (MHC) class II, CD86, and IL-12 expression. The Adv/IL-10 transduced DCs were phenotypically unique, characterized by suppression of IL-12 expression, failure to stimulate Th1 or Th2 cytokine responses, and retained capacity to endocytose antigen. Importantly, Adv/IL-10-transduced DCs were biologically active in vivo, in that administration of these DCs into mice before a generalized peritonitis significantly improved survival. We conclude that Adv/IL-10 transduction of DCs provides an efficient means to modulate DC function. The capacity to modify DCs by adenoviral expression of IL-10 may provide a novel ex vivo or in vivo approach to mitigate acute and chronic inflammatory diseases like sepsis.