title: B and T lymphocyte attenuator down-regulation by HIV-1 depends on type I interferon and contributes to T-cell hyperactivation.
abstract: BACKGROUND
  Nonspecific T-cell hyperactivation is the main driving force for human immunodeficiency virus (HIV)-1 disease progression, but the reasons why the excess immune response is 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 and function. Infection and blockade assays were used to dissect the factors that influenced BTLA signaling in vitro.
  
  
  RESULTS
  BTLA expression on overall CD4(+) and CD8(+) T cells was progressively decreased in HIV-1 infection, which was directly correlated with disease progression and CD4(+) T-cell differentiation and activation. BTLA(+)CD4(+) T cells from HIV-1-infected patients also displayed an altered immune status, which was indicated by reduced expression of naive markers but increased activation and exhaustion markers. Cross-linking of BTLA can substantially decrease CD4(+) T-cell activation in vitro. This responsiveness of CD4(+) T cells to BTLA-mediated inhibitory signaling was further found to be impaired in HIV-1-infected patients. Furthermore, HIV-1 NL4-3 down-regulated BTLA expression on CD4(+) T cells dependent on plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α. Blockade of IFN-α or depletion of pDCs prevents HIV-1-induced BTLA down-regulation.
  
  
  CONCLUSIONS
  HIV-1 infection potentially impairs BTLA-mediated signaling dependent on pDC-derived IFN-α, which may contribute to broad T-cell hyperactivation induced by chronic HIV-1 infection.
authors: Research Center for Biological Therapy, Beijing 302 Hospital, Institute of Biophysics, Chinese Academy of Science, Beijing, China.
authors: Zheng
authors: Z
authors: Zhang
authors: Xiangsheng
authors: X
authors: Xu
authors: Jiyun
authors: J
authors: Lu
authors: Shuye
authors: S
authors: Zhang
authors: Lanlan
authors: L
authors: Gu
authors: Junliang
authors: J
authors: Fu
authors: Lei
authors: L
authors: Jin
authors: Haiying
authors: H
authors: Li
authors: Min
authors: M
authors: Zhao
authors: Jiyuan
authors: J
authors: Zhang
authors: Hao
authors: H
authors: Wu
authors: Lishan
authors: L
authors: Su
authors: Yang-Xin
authors: YX
authors: Fu
authors: Fu-Sheng
authors: FS
authors: Wang
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