Impact of cytotoxic-T-lymphocyte memory induction without virus-specific CD4+ T-Cell help on control of a simian immunodeficiency virus challenge in rhesus macaques.
J Virol
; 83(18): 9339-46, 2009 Sep.
Article
em En
| MEDLINE
| ID: mdl-19587045
ABSTRACT
Despite many efforts to develop AIDS vaccines eliciting virus-specific T-cell responses, whether induction of these memory T cells by vaccination before human immunodeficiency virus (HIV) exposure can actually contribute to effective T-cell responses postinfection remains unclear. In particular, induction of HIV-specific memory CD4(+) T cells may increase the target cell pool for HIV infection because the virus preferentially infects HIV-specific CD4(+) T cells. However, virus-specific CD4(+) helper T-cell responses are thought to be important for functional CD8(+) cytotoxic-T-lymphocyte (CTL) induction in HIV infection, and it has remained unknown whether HIV-specific memory CD8(+) T cells induced by vaccination without HIV-specific CD4(+) T-cell help can exert effective responses after virus exposure. Here we show the impact of CD8(+) T-cell memory induction without virus-specific CD4(+) T-cell help on the control of a simian immunodeficiency virus (SIV) challenge in rhesus macaques. We developed a prophylactic vaccine by using a Sendai virus (SeV) vector expressing a single SIV Gag(241-249) CTL epitope fused with enhanced green fluorescent protein (EGFP). Vaccination resulted in induction of SeV-EGFP-specific CD4(+) T-cell and Gag(241-249)-specific CD8(+) T-cell responses. After a SIV challenge, the vaccinees showed dominant Gag(241-249)-specific CD8(+) T-cell responses with higher effector memory frequencies in the acute phase and exhibited significantly reduced viral loads. These results demonstrate that virus-specific memory CD8(+) T cells induced by vaccination without virus-specific CD4(+) T-cell help could indeed facilitate SIV control after virus exposure, indicating the benefit of prophylactic vaccination eliciting virus-specific CTL memory with non-virus-specific CD4(+) T-cell responses for HIV control.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
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Síndrome de Imunodeficiência Adquirida dos Símios
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Vírus da Imunodeficiência Símia
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Memória Imunológica
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article