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Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4.

Publication ,  Journal Article
Cisco, RM; Abdel-Wahab, Z; Dannull, J; Nair, S; Tyler, DS; Gilboa, E; Vieweg, J; Daaka, Y; Pruitt, SK
Published in: J Immunol
June 1, 2004

Maturation of dendritic cells (DC) is critical for the induction of Ag-specific immunity. Ag-loaded DC matured with LPS, which mediates its effects by binding to Toll-like receptor 4 (TLR4), induce Ag-specific CTL in vitro and in vivo in animal models. However, clinical use of LPS is limited due to potential toxicity. Therefore, we sought to mimic the maturation-inducing effects of LPS on DC by stimulating TLR4-mediated signaling in the absence of exogenous LPS. We developed a constitutively active TLR4 (caTLR4) and demonstrated that transfection of human DC with RNA encoding caTLR4 led to IL-12 and TNF-alpha secretion. Transfection with caTLR4 RNA also induced a mature DC phenotype. Functionally, transfection of DC with caTLR4 RNA enhanced allostimulation of CD4(+) T cells. DC transfected with RNA encoding the MART (Melan-A/MART-1) melanoma Ag were then used to stimulate T cells in vitro. Cotransfection of these DC with caTLR4 RNA enhanced the generation of MART-specific CTL. This CTL activity was superior to that seen when DC maturation was induced using either LPS or a standard mixture of cytokines (TNF-alpha, IL-6, IL-1beta, and PGE(2)). We conclude that transfection of DC with RNA encoding a functional signaling protein, such as caTLR4, may provide a new tool for studying TLR signaling in DC and may be a promising approach for the induction of DC maturation for tumor immunotherapy.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

June 1, 2004

Volume

172

Issue

11

Start / End Page

7162 / 7168

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Transfection
  • Toll-Like Receptors
  • Toll-Like Receptor 4
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Cell Surface
  • RNA
  • Membrane Glycoproteins
  • Lipopolysaccharides
 

Citation

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Cisco, R. M., Abdel-Wahab, Z., Dannull, J., Nair, S., Tyler, D. S., Gilboa, E., … Pruitt, S. K. (2004). Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4. J Immunol, 172(11), 7162–7168. https://doi.org/10.4049/jimmunol.172.11.7162
Cisco, Robin M., Zeinab Abdel-Wahab, Jens Dannull, Smita Nair, Douglas S. Tyler, Eli Gilboa, Johannes Vieweg, Yehia Daaka, and Scott K. Pruitt. “Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4.J Immunol 172, no. 11 (June 1, 2004): 7162–68. https://doi.org/10.4049/jimmunol.172.11.7162.
Cisco RM, Abdel-Wahab Z, Dannull J, Nair S, Tyler DS, Gilboa E, et al. Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4. J Immunol. 2004 Jun 1;172(11):7162–8.
Cisco, Robin M., et al. “Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4.J Immunol, vol. 172, no. 11, June 2004, pp. 7162–68. Pubmed, doi:10.4049/jimmunol.172.11.7162.
Cisco RM, Abdel-Wahab Z, Dannull J, Nair S, Tyler DS, Gilboa E, Vieweg J, Daaka Y, Pruitt SK. Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4. J Immunol. 2004 Jun 1;172(11):7162–7168.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

June 1, 2004

Volume

172

Issue

11

Start / End Page

7162 / 7168

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Transfection
  • Toll-Like Receptors
  • Toll-Like Receptor 4
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Cell Surface
  • RNA
  • Membrane Glycoproteins
  • Lipopolysaccharides