B and T Lymphocyte Attenuator Down-regulation by HIV-1 Depends on Type I Interferon and Contributes to T-Cell Hyperactivation

摘要: Background. Nonspecific T-cell hyperactivation is the main driving force for human immunodeficiency virus (HIV)–1 disease progression, but reasons why excess immune response not properly shut off are poorly defined. Methods. Eighty-five HIV-1–infected individuals were enrolled to characterize B and T lymphocyte attenuator (BTLA) expression function. Infection blockade assays used dissect factors that influenced BTLA signaling in vitro. Results. BTLA on overall CD4+ CD8+ cells was progressively decreased HIV-1 infection, which directly correlated with progression differentiation activation. BTLA+CD4+ from patients also displayed an altered status, indicated by reduced of naive markers increased activation exhaustion markers. Cross-linking can substantially decrease vitro. This responsiveness BTLA-mediated inhibitory further found be impaired patients. Furthermore, NL4-3 down-regulated dependent plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α. Blockade IFN-α or depletion pDCs prevents HIV-1-induced down-regulation. Conclusions. HIV-1 infection potentially impairs pDC-derived IFN-α, may contribute broad induced chronic infection.