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

Geoffrey 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 Citations (Scopus)

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

Fingerprint

CD40 Ligand
T-cells
Macaca
Cell proliferation
Ligands
Viruses
Molecules
Vaccines
Cells
DNA Vaccines
Tumor Necrosis Factor Receptors
Immunosuppressive Agents
Tumor Necrosis Factors
Glucocorticoids
Cell Proliferation
Assays
Plasmids
T-Lymphocytes
Tumor Necrosis Factor-alpha
Simian Immunodeficiency Virus

ASJC Scopus subject areas

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

Cite this

Stone, G., Barzee, S., Snarsky, V., Spina, C. A., Lifson, J. D., Pillai, V. K. B., ... 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

Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro. / Stone, Geoffrey; Barzee, Suzanne; Snarsky, Victoria; Spina, Celsa A.; Lifson, Jeffrey D.; Pillai, Vinod Kumar Bhaskara; Amara, Rama Rao; Villinger, François; Kornbluth, Richard S.

In: Clinical and Vaccine Immunology, Vol. 13, No. 11, 01.11.2006, p. 1223-1230.

Research output: Contribution to journalArticle

Stone, G, Barzee, S, Snarsky, V, Spina, CA, Lifson, JD, Pillai, VKB, Amara, RR, Villinger, F & Kornbluth, RS 2006, 'Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro', Clinical and Vaccine Immunology, vol. 13, no. 11, pp. 1223-1230. https://doi.org/10.1128/CVI.00198-06
Stone, Geoffrey ; Barzee, Suzanne ; Snarsky, Victoria ; Spina, Celsa A. ; Lifson, Jeffrey D. ; Pillai, Vinod Kumar Bhaskara ; Amara, Rama Rao ; Villinger, François ; Kornbluth, Richard S. / Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro. In: Clinical and Vaccine Immunology. 2006 ; Vol. 13, No. 11. pp. 1223-1230.
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