4-1BB and OX40 stimulation enhance CD8 and CD4 T-cell responses to a DNA prime, poxvirus boost vaccine

Michael W. Munks, Dan V. Mourich, Robert S. Mittler, Andrew D. Weinberg, Ann B. Hill

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

4-1BB (CD137) is a tumour necrosis factor receptor (TNFR) family member, expressed primarily on CD8 T cells after activation. Signalling through 4-1BB has been reported to enhance CD8 T-cell expansion and to protect activated CD8 T cells from death, resulting in an enlarged memory population. Although stimulating 4-1BB has been shown to significantly improve the immune response to weak immunogens such as tumours, little is known about its effect on the CD8 T-cell response to a powerful viral vector such as vaccinia. To test 4-1BB's ability to improve the marine CD8 T cell response to a DNA prime, poxvirus boost vaccine, similar to those used for human immunodeficiency virus and simian immunodeficiency virus vaccines, we administered 4-1BB agonist antibody at the time of the poxvirus boost. 4-1BB stimulation increased the number of functional memory CD8 T cells by two- to fourfold. However, we saw a similar enhancement at the peak of the response and in the memory phase, thus we found no evidence in the context of virus infection that 4-1BB stimulation could increase the percentage of CD8 T cells that survive the acute activation phase to become memory cells. OX40 (CD134) is an analogous TNFR family member expressed primarily on activated CD4 T cells. OX40 stimulation increased the number of antigen-specific CD4 T cells approximately threefold. Stimulating both 4-1BB and OX40 enhanced the CD8 T-cell response more than 4-1BB alone. Thus stimulating these receptors can improve the response to a powerful virus vector, and may be useful in vaccine development.

Original languageEnglish (US)
Pages (from-to)559-566
Number of pages8
JournalImmunology
Volume112
Issue number4
DOIs
StatePublished - Aug 2004

Keywords

  • Costimulation
  • T lymphocytes
  • Viral

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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