Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption.
Nat Immunol
; 25(10): 1900-1912, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-39266691
ABSTRACT
Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac239-infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8+ T cells in lymph nodes and reduced expression of BCL-2 in CD4+ T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4+ and CD8+ T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Imunodeficiência Adquirida dos Símios
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Vírus da Imunodeficiência Símia
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Interleucina-10
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Linfócitos T CD8-Positivos
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Carga Viral
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Receptor de Morte Celular Programada 1
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Macaca mulatta
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article