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

Robin M. Cisco, Zeinab Abdel-Wahab, Jens Dannull, Smita Nair, Douglas Tyler, Eli Gilboa, Johannes Vieweg, Yehia Daaka, Scott K. Pruitt

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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-α 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-α, IL-6, IL-1β, and PGE2). 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.

Original languageEnglish (US)
Pages (from-to)7162-7168
Number of pages7
JournalJournal of Immunology
Volume172
Issue number11
StatePublished - Jun 1 2004
Externally publishedYes

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Toll-Like Receptor 4
Dendritic Cells
Transfection
RNA
MART-1 Antigen
T-Lymphocytes
Interleukin-12
Interleukin-1
Dinoprostone
Immunotherapy
Immunity
Melanoma
Interleukin-6
Animal Models

ASJC Scopus subject areas

  • Immunology

Cite this

Cisco, R. M., Abdel-Wahab, Z., Dannull, J., Nair, S., Tyler, D., Gilboa, E., ... Pruitt, S. K. (2004). Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4. Journal of Immunology, 172(11), 7162-7168.

Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4. / Cisco, Robin M.; Abdel-Wahab, Zeinab; Dannull, Jens; Nair, Smita; Tyler, Douglas; Gilboa, Eli; Vieweg, Johannes; Daaka, Yehia; Pruitt, Scott K.

In: Journal of Immunology, Vol. 172, No. 11, 01.06.2004, p. 7162-7168.

Research output: Contribution to journalArticle

Cisco, RM, Abdel-Wahab, Z, Dannull, J, Nair, S, Tyler, D, Gilboa, E, Vieweg, J, Daaka, Y & Pruitt, SK 2004, 'Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4', Journal of Immunology, vol. 172, no. 11, pp. 7162-7168.
Cisco, Robin M. ; Abdel-Wahab, Zeinab ; Dannull, Jens ; Nair, Smita ; Tyler, Douglas ; Gilboa, Eli ; Vieweg, Johannes ; Daaka, Yehia ; Pruitt, Scott K. / Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4. In: Journal of Immunology. 2004 ; Vol. 172, No. 11. pp. 7162-7168.
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