Vector-driven hyperexpression of a triad of costimulatory molecules confers enhanced T-cell stimulatory capacity to DC precursors

Ariel N. Rad, Jeffrey Schlom, James W. Hodge

Research output: Contribution to journalArticle

Abstract

Activation of T cells requires at least two signals: signal 1, via the T-cell receptor, and signal 2, in which a costimulatory molecule on the antigen presenting cell (APC) interacts with a ligand on the T cell. Dendritic cells (DCs) are the most potent APCs in part due to their expression of costimulatory molecules. DCs, however, constitute only a minor percentage of APCs in the body, and the in vitro preparation of DCs is both costly and time consuming. The studies reported here demonstrate that one can utilize other APCs, such as bone marrow progenitor cells (BMPCs) and make them markedly more effective as APCs; this was accomplished by their infection with recombinant poxviruses (either the replication-defective avipox or vaccinia), which contain transgenes for a triad of costimulatory molecules (B7-1, ICAM-1 and LFA-3, designated TRICOM). APCs infected with TRICOM vectors are shown to significantly enhance the activation of both naive and effector CD4+ and CD8+ T-cell populations. The use of TRICOM vectors in vaccine strategies is discussed.

Original languageEnglish (US)
Pages (from-to)43-57
Number of pages15
JournalCritical Reviews in Oncology/Hematology
Volume39
Issue number1-2
DOIs
StatePublished - Jul 3 2001
Externally publishedYes

Keywords

  • Bone marrow
  • Costimulation
  • Fowlpox
  • T cells
  • Vaccine
  • Vaccinia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Geriatrics and Gerontology

Fingerprint Dive into the research topics of 'Vector-driven hyperexpression of a triad of costimulatory molecules confers enhanced T-cell stimulatory capacity to DC precursors'. Together they form a unique fingerprint.

  • Cite this