Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity.
Proc Natl Acad Sci U S A
; 106(9): 3330-5, 2009 Mar 03.
Article
em En
| MEDLINE
| ID: mdl-19211791
ABSTRACT
Current influenza A virus vaccines do not generate significant immunity against serologically distinct influenza A virus subtypes and would thus be ineffective in the face of a pandemic caused by a novel variant emerging from, say, a wildlife reservoir. One possible solution would be to modify these vaccines so that they prime cross-reactive CD8(+) cytotoxic T lymphocytes (CTL) cell-mediated immunity directed at conserved viral epitopes. A further strategy is to use novel adjuvants, such as the immunomodulatory glycolipid alpha-galactosylceramide (alpha-GalCer). We show here that giving alpha-GalCer with an inactivated influenza A virus has the paradoxical effect of diminishing acute CTL immunity via natural killer T (NKT) cell-dependent expression of indoleamine 2,3-dioxygenase (IDO), an important mediator of immune suppression, while at the same time promoting the survival of long-lived memory CTL populations capable of boosting protection against heterologous influenza A virus challenge. This enhancement of memory was likely due to the alpha-GalCer-induced upregulation of prosurvival genes, such as bcl-2, and points to the potential of alpha-GalCer as an adjuvant for promoting optimal, vaccine-induced CD8(+) T cell memory.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vacinas contra Influenza
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Ativação Linfocitária
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Linfócitos T Citotóxicos
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Imunização Secundária
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Vírus da Influenza A Subtipo H3N2
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Células T Matadoras Naturais
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Memória Imunológica
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article