Enhanced activation of T cells by dendritic cells engineered to hyperexpress a triad of costimulatory molecules

James W. Hodge, Ariel N. Rad, Douglas W. Grosenbach, Helen Sabzevari, Alicia Gómez Yafal, Linda Gritz, Jeffrey Schlom

Research output: Contribution to journalArticle

Abstract

Background: Activation and proliferation of T cells are essential for a successful cellular immune response to an antigen. Antigen-presenting cells (APCs) activate T cells through a two-signal mechanism. The first signal is antigen specific and causes T cells to enter the cell cycle. The second signal involves a costimulatory molecule that interacts with a ligand on the T-cell surface and leads to T-cell cytokine production and their proliferation. Dendritic cells express several costimulatory molecules and are believed to be the most potent APCs. Two recombinant poxvirus vectors (replication-defective avipox [fowlpox; rF] and a replication-competent vaccinia [rV]) have been engineered to express a triad of costimulatory molecules (B7-1, intercellular adhesion molecule-1, and leukocyte function-associated antigen 3; designated TRICOM). This study was designed to determine if dendritic cells infected with these vectors would have an enhanced capacity to stimulate T-cell responses. Methods: Murine dendritic cells (of both intermediate maturity and full maturity) were infected with rF-TRICOM or rV-TRICOM and were used in vitro to stimulate naive T cells with the use of a pharmacologic agent as signal 1, to stimulate T cells in allospecific mixed lymphocyte cultures, and to stimulate CD8+ T cells specific for a peptide from the ovalbumin (OVA) protein. In addition, dendritic cells infected with TRICOM vectors were pulsed with OVA peptide and used to vaccinate mice to examine T-cell responses in vivo. All statistical tests were two-sided. Results: Dendritic cells infected with either rF-TRICOM or rV-TRICOM were found to greatly enhance naive T-cell activation (P

Original languageEnglish (US)
Pages (from-to)1228-1239
Number of pages12
JournalJournal of the National Cancer Institute
Volume92
Issue number15
StatePublished - Aug 2 2000
Externally publishedYes

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Dendritic Cells
T-Lymphocytes
Vaccinia
Ovalbumin
Antigen-Presenting Cells
Fowlpox
CD80 Antigens
Poxviridae
Antigens
Peptides
Histocompatibility Antigens Class II
Intercellular Adhesion Molecule-1
Cellular Immunity
Cell Cycle
Leukocytes
Lymphocytes
Cytokines
Ligands

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hodge, J. W., Rad, A. N., Grosenbach, D. W., Sabzevari, H., Gómez Yafal, A., Gritz, L., & Schlom, J. (2000). Enhanced activation of T cells by dendritic cells engineered to hyperexpress a triad of costimulatory molecules. Journal of the National Cancer Institute, 92(15), 1228-1239.

Enhanced activation of T cells by dendritic cells engineered to hyperexpress a triad of costimulatory molecules. / Hodge, James W.; Rad, Ariel N.; Grosenbach, Douglas W.; Sabzevari, Helen; Gómez Yafal, Alicia; Gritz, Linda; Schlom, Jeffrey.

In: Journal of the National Cancer Institute, Vol. 92, No. 15, 02.08.2000, p. 1228-1239.

Research output: Contribution to journalArticle

Hodge, JW, Rad, AN, Grosenbach, DW, Sabzevari, H, Gómez Yafal, A, Gritz, L & Schlom, J 2000, 'Enhanced activation of T cells by dendritic cells engineered to hyperexpress a triad of costimulatory molecules', Journal of the National Cancer Institute, vol. 92, no. 15, pp. 1228-1239.
Hodge, James W. ; Rad, Ariel N. ; Grosenbach, Douglas W. ; Sabzevari, Helen ; Gómez Yafal, Alicia ; Gritz, Linda ; Schlom, Jeffrey. / Enhanced activation of T cells by dendritic cells engineered to hyperexpress a triad of costimulatory molecules. In: Journal of the National Cancer Institute. 2000 ; Vol. 92, No. 15. pp. 1228-1239.
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