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

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
批准号:
9065380
负责人:
Anjie Zhen
金额:
$6.0万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-01 至 2017-06-30

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英文摘要
 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.
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