An engineered novel lentivector specifically transducing dendritic cells and eliciting robust HBV-specific CTL response by upregulating autophagy in T cells. Issue 10 (19th May 2018)

• Record Type: Journal Article
• Authors: Ma, Siyuan; Chen, Xiaohua; Tan, Quanhui; Li, Dan; Dai, Shenglan; Wu, Shanshan; Yu, Yongsheng; Zang, Guoqing; Tang, Zhenghao
• Is Part Of: Cell cycle. Volume 17:Issue 10(2018)
• Page Start: 1220
• Page End: 1234
• Publication Date: 2018-05-19
• Subjects: Dendritic cell (DC)-targeting lentivector -- cytotoxic T lymphocyte (CTL) -- autophagy; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2018.1471312
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Dendritic cells (DCs) play a predominant role in initiating cell immune responses. Here we generated a DC-targeting lentiviral vector (LVDC-UbHBcAg-LIGHT) and evaluated its capacity to elicit HBV-specific cytotoxic T lymphocyte (CTL) responses. DC-SIGN-mediated specific transduction using this construct was confirmed in DC-SIGN-expressing 293T cells and ex vivo -cultured bone marrow cells. LVDC-UbHBcAg-LIGHT-loaded DCs were highly effective in inducing HBV-specific CTLs. Mechanistic studies demonstrated autophagy blocking led to a significant increase in apoptosis and obvious inhibition of CD8 + T cells entry into S-phase, correspondingly attenuated LVDC-UbHBcAg-LIGHT-loaded DC-induced T cell responses. This observation was supported by accumulation of pro-apoptotic proteins and the main negative cell cycle regulator-CDKN1B that otherwise would be degraded in activated T cells where autophagy preferentially occured. Our findings revealed an important role of autophagy in the activation of T cells and suggested LVDC-UbHBcAg-LIGHT may potentially be used as a therapeutic strategy to combat persistent HBV infection with higher security.