TY - JOUR
T1 - Increased survival in sepsis by in vivo adenovirus-induced expression of IL-10 in dendritic cells
AU - Oberholzer, Andreas
AU - Oberholzer, Caroline
AU - Bahjat, Keith S.
AU - Ungaro, Ricardo
AU - Tannahill, Cynthia L.
AU - Murday, Michelle
AU - Bahjat, Frances R.
AU - Abouhamze, Zaher
AU - Tsai, Van
AU - LaFace, Drake
AU - Hutchins, Beth
AU - Moldawer, Lyle L.
AU - Clare-Salzler, Michael J.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002/4/1
Y1 - 2002/4/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.168.7.3412
DO - 10.4049/jimmunol.168.7.3412
M3 - Article
C2 - 11907099
AN - SCOPUS:0036533584
SN - 0022-1767
VL - 168
SP - 3412
EP - 3418
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -