Functional modification of dendritic cells with recombinant adenovirus encoding interleukin 10 for the treatment of sepsis.
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.
Oberholzer
Andreas
A
Department of Surgery, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Oberholzer
Caroline
C
Efron
Philip A
PA
Scumpia
Philip O
PO
Uchida
Takefumi
T
Bahjat
Keith
K
Ungaro
Ricardo
R
Tannahill
Cynthia L
CL
Murday
Michelle
M
Bahjat
Frances R
FR
Tsai
Van
V
Hutchins
Beth
B
Moldawer
Lyle L
LL
Laface
Drake
D
Clare-Salzler
Michael J
MJ
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D018805:Sepsis / Q000378:metabolism / Q000628:therapy*; D013601:T-Lymphocytes / Q000166:cytology; D018417:Th1 Cells; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
D015703:Antigens, CD; D051940:B7-2 Antigen; D017252:CD3 Complex; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor