Department Name

Functional modification of dendritic cells with recombinant adenovirus encoding IL-10 for suppression of pro-inflammatory T cell immunity

Abstract:
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 IL-10 could alter their T cell stimulatory function. Murine bone marrow-derived DC's were transduced with adenoviral vectors encoding human IL-10 (AdV/IL-10) or GFP (AdV/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 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 capable of suppressing T cell immunity in vivo, in that administration of these DCs into mice prior to a generalized peritonitis significantly improved survival of the mice. 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. 

Manuscript	Submitted to Journal of Immunotherapy
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Tables	1  Transduction efficiency of mature (class II and CD86 high) and immature (class II and CD86 low) DC (n = 5) induced with 1010 particles/ml of Adv/gfp. To induce maturation, DCs were stimulated with 1 mg/ml LPS 24 hours prior to transduction with the Adv/gfp.