Accumulation of a potent gammadelta T-cell stimulator after deletion of the lytB gene in Escherichia coli.
Immunology
; 106(2): 200-11, 2002 Jun.
Article
em En
| MEDLINE
| ID: mdl-12047749
ABSTRACT
Activation of human Vgamma9/Vdelta2 T cells by many pathogens depends on the presence of small phosphorylated non-peptide compounds derived from the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis. We here demonstrate that in Escherichia coli mutants deficient in lytB, an essential gene of the MEP pathway, a potent Vgamma9/Vdelta2 T-cell activator accumulates by a factor of approximately 150 compared to wild-type E. coli. The compound responsible for the strong immunogenicity of this E. coli mutant was subsequently characterized and identified as a small pyrophosphorylated metabolite, with a molecular mass of 262 Da, derived from the MEP pathway. Stimulation of human peripheral blood mononuclear cells (PBMC) with extracts prepared from the lytB-deficient E. coli mutant led to upregulation of T-cell activation markers on the surface of Vgamma9/Vdelta2 T cells as well as proliferation and expansion of Vgamma9/Vdelta2 T cells. This response was dependent on costimulatory growth factors, such as interleukin (IL)-2, IL-15 and IL-21. Significant levels of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were secreted in the presence of IL-2 and IL-15, but not in the presence of IL-21, demonstrating that proliferating phosphoantigen-reactive Vgamma9/Vdelta2 T cells do not necessarily produce proinflammatory cytokines.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxirredutases
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Proteínas de Bactérias
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Ativação Linfocitária
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Subpopulações de Linfócitos T
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Receptores de Antígenos de Linfócitos T gama-delta
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Proteínas de Escherichia coli
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Eritritol
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Escherichia coli
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article