Increased survival in sepsis by in vivo adenovirus-induced expression of IL-10 in dendritic cells

Andreas Oberholzer, Caroline Oberholzer, Keith S. Bahjat, Ricardo Ungaro, Cynthia L. Tannahill, Michelle Murday, Frances R. Bahjat, Zaher Abouhamze, Van Tsai, Drake LaFace, Beth Hutchins, Lyle L. Moldawer, Michael J. Clare-Salzler

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

The dendritic cell (DC) is the most potent APC of the immune system, capable of stimulating naive T cells to proliferate and differentiate into effector T cells. Recombinant adenovirus (Adv) readily transduces DCs in vitro allowing directed delivery of transgenes that modify DC function and immune responses. In this study we demonstrate that footpad injection of a recombinant Adv readily targets transduction of myeloid and lymphoid DCs in the draining popliteal lymph node, but not in other lymphoid organs. Popliteal DCs transduced with an empty recombinant Adv undergo maturation, as determined by high MHC class II and CD86 expression. However, transduction with vectors expressing human IL-10 limit DC maturation and associated T cell activation in the draining lymph node. The extent of IL-10 expression is dose dependent; transduction with low particle numbers (105) yields only local expression, while transduction with higher particle numbers (107 and 1010) leads additionally to IL-10 appearance in the circulation. Furthermore, local DC expression of human IL-10 following in vivo transduction with low particle numbers (105) significantly improves survival following cecal ligation and puncture, suggesting that compartmental modulation of DC function profoundly alters the sepsis-induced immune response.

Original languageEnglish (US)
Pages (from-to)3412-3418
Number of pages7
JournalJournal of Immunology
Volume168
Issue number7
DOIs
StatePublished - Apr 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Oberholzer, A., Oberholzer, C., Bahjat, K. S., Ungaro, R., Tannahill, C. L., Murday, M., Bahjat, F. R., Abouhamze, Z., Tsai, V., LaFace, D., Hutchins, B., Moldawer, L. L., & Clare-Salzler, M. J. (2002). Increased survival in sepsis by in vivo adenovirus-induced expression of IL-10 in dendritic cells. Journal of Immunology, 168(7), 3412-3418. https://doi.org/10.4049/jimmunol.168.7.3412