Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity.
Proc Natl Acad Sci U S A
; 112(31): E4256-63, 2015 Aug 04.
Article
en En
| MEDLINE
| ID: mdl-26195744
ABSTRACT
Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8(+) T-cell responses have been extensively studied, the breadth and specificity of CD4(+) T-cell responses remains to be defined. Here we define HLA-restricted CD4(+) T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENV-specific CD4(+) T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1(+) Eomesodermin(+) perforin(+) granzyme B(+) CD45RA(+) CD4 CTL phenotype. Importantly, these cells correlated with a protective HLA DR allele, and we demonstrate that these cells have direct ex vivo DENV-specific cytolytic activity. We speculate that cytotoxic dengue-specific CD4(+) T cells may play a role in the control of dengue infection in vivo, and this immune correlate may be a key target for dengue virus vaccine development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
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Polaridad Celular
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Receptores de Quimiocina
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Citotoxicidad Inmunológica
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Dengue
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Virus del Dengue
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Inmunidad
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2015
Tipo del documento:
Article