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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dengue virus infection elicits highly polarized CX3CR1(+) cytotoxic CD4(+) T cells associated with protective immunity
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Dengue virus infection elicits highly polarized CX3CR1(+) cytotoxic CD4(+) T cells associated with protective immunity

机译：Dengue virus infection elicits highly polarized CX3CR1(+) cytotoxic CD4(+) T cells associated with protective immunity

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摘要

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.

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