Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro

Geoffrey W. Stone, Suzanne Barzee, Victoria Snarsky, Celsa A. Spina, Jeffrey D. Lifson, Vinod Kumar Bhaskara Pillai, Rama Rao Amara, François Villinger, Richard S. Kornbluth

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

CD40 ligand (CD40L) and GITR ligand (glucocorticoid-induced tumor necrosis factor receptor-related protein ligand [GITRL]) are tumor necrosis factor superfamily molecules that can be used as vaccine adjuvants. In a previous human immunodeficiency virus (HIV) DNA vaccine study in mice, we found that plasmids expressing multimeric soluble forms of trimeric CD40L (i.e., many trimers) were stronger activators of CD8+ T-cell responses than were single-trimer soluble forms or the natural membrane-bound molecule. This report describes similar multimeric soluble molecules that were constructed for studies in macaques. Both two-trimer and four-trimer forms of macaque CD40L were active in B-cell proliferation assays using macaque and human cells. With human cells, four-trimer macaque GITRL costimulated CD4+ T-cell proliferation and abrogated the immunosuppressive effects of CD4+ CD25+ regulatory T cells on a mixed leukocyte reaction. These molecular adjuvants provide new tools for vaccine development in the simian immunodeficiency virus system and other macaque models.

Original languageEnglish (US)
Pages (from-to)1223-1230
Number of pages8
JournalClinical and Vaccine Immunology
Volume13
Issue number11
DOIs
StatePublished - Nov 1 2006

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Stone, G. W., Barzee, S., Snarsky, V., Spina, C. A., Lifson, J. D., Pillai, V. K. B., Amara, R. R., Villinger, F., & Kornbluth, R. S. (2006). Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro. Clinical and Vaccine Immunology, 13(11), 1223-1230. https://doi.org/10.1128/CVI.00198-06