Characterization and restoration of exhausted immune responses in humanized Bone marrow-liver-thymus (BLT) mice infected with HIV-1

感染 HIV-1 的人源化骨髓-肝-胸腺 (BLT) 小鼠的衰竭免疫反应的表征和恢复

基本信息

  • 批准号:
    9065380
  • 负责人:
  • 金额:
    $ 6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-07-01 至 2017-06-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Cellular immune responses play a crucial role in controlling viral replication in HIV- infected individuals. However, HIV virus adopts numerous mechanisms to evade the immune system and the host ultimately fails to control the viral replication leading to development of AIDS. Chronic inflammation and ongoing viral replication may lead to immune exhaustion, which is characterized by poor anti-viral responses against HIV. The major aims of the proposal are to 1) characterize the mechanisms of immune dysfunction and exhaustion during chronic HIV infection and 2) explore various strategies to restore or prevent immune exhaustion and improve viral control using the humanized mice model. The strategies include 1) targeting activation inhibitory molecules Tim-3 and PD-1 signaling by antibody blockade or shRNA knock down; and 2) targeting persistent type I IFN signaling to reduce the production of immunosuppressive factors that contribute to immune exhaustion. This study will identify underlying mechanisms for T cell exhaustion and provide key information for future immune based therapies aimed at treating chronic HIV infection.


项目成果

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