Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses: Comparison with B7.1 and 4-1BBL

Lena Serghides, Jacob Bukczynski, Tao Wen, Chao Wang, Jean Pierre Routy, Mohamed Rachid Boulassel, Rafick Pierre Sekaly, Mario Ostrowski, Nicole F. Bernard, Tania H. Watts

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Abstract

CTL are important effectors of antiviral immunity. Designing adjuvants that can induce strong cytotoxic T cell responses in humans would greatly improve the effectiveness of an antiviral vaccination or therapeutic strategy. Recent evidence suggests that, in addition to its well-established role in costimulation of CD4 T cell responses, OX40L (CD134) can directly costimulate mouse CD8 T cells. In this study, we evaluated the role of OX40L in costimulation of human antiviral CD8 T cell responses and compared it with two other important costimulators, B7.1 (CD80) and 4-1BBL (CD137L). Delivery of OX40L to human monocytes using a recombinant replication-defective adenovirus led to greater expansion, up-regulation of perforin, enhanced cytolytic activity, and increased numbers of IFN-γ-and TNF-α-producing antiviral memory CD8 T cells in cultures of total T eels. Synergistic or additive effects were observed when OX40L costimulation was combined with 4-1BBL (CD137L) or B7.1 (CD80) costimulation. In total T cell cultures, at low Ag dose, 4-1BBL provided the most potent costimulus for influenza-specific CD8 T cell expansion, followed by B7.1 (CD80) and then OX40L. For isolated CD8 T cells, 4-1BBL was also the most consistent costimulator, followed by B7.1. In contrast, OX40L showed efficacy in direct activation of memory CD8 T cells in only one of seven donors. Thus, OX40L costimulates human antiviral memory CD8 T cell responses largely through indirect effects and can enhance anti-influenza, anti-EBV, and anti-HIV responses, particularly in combination with 4-1BBL or B7.

Original languageEnglish
Pages (from-to)6368-6377
Number of pages10
JournalJournal of Immunology
Volume175
Issue number10
Publication statusPublished - Nov 15 2005

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ASJC Scopus subject areas

  • Immunology

Cite this

Serghides, L., Bukczynski, J., Wen, T., Wang, C., Routy, J. P., Boulassel, M. R., ... Watts, T. H. (2005). Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses: Comparison with B7.1 and 4-1BBL. Journal of Immunology, 175(10), 6368-6377.