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


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.

SUBMITTER: Stone GW 

PROVIDER: S-EPMC1656546 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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

Stone Geoffrey W GW   Barzee Suzanne S   Snarsky Victoria V   Spina Celsa A CA   Lifson Jeffrey D JD   Pillai Vinod Kumar Bhaskara VK   Amara Rama Rao RR   Villinger François F   Kornbluth Richard S RS  

Clinical and vaccine immunology : CVI 20060920 11


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-bo  ...[more]

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