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Master Thesis

Potentiel immuno-thérapeutique des pDCs dans l'hépatite B chronique

Abstract : The immune control of HBV infection is essential for viral clearance. Restoring functional anti‐HBV immunity is therefore a promising immunotherapeutic approach. Plasmacytoid dendritic cells (pDC) play a crucial role in anti‐viral immunity due to their ability to capture and process viral antigens and induce immune responses. We therefore investigated for the first time the potential of pDCs in triggering anti‐viral immunity against HBV. We used a pDC line loaded with HLA‐A*0201-restricted peptides derived from HBc/HBs antigens to amplify specific T cells ex-vivo from chronic HBV patients and established an Hepato-HuPBL humanized mouse model to address the therapeutic potential of the strategy. Stimulation of PBMC or liver-infiltrated lymphocytes from HLA‐A*0201+ chronic HBV patients by the HBc peptide-loaded pDC line elicited HBV-specific CD8 T cells in 45.8% of cases. The specific T cells of the "responder" group were able to express CD107 upon restimulation and lyse infected hepatocytes in-vitro. The "non-responder" group of patients was characterised by the presence of HBeAg or higher level of regulatory T cells. The therapeutic efficacy of the pDC-vaccine was evaluated in immunodeficient NOD-SCID2m-/- mice reconstituted with HBV patients' PBMC and xenotransplanted with human HBV-infected hepatocytes. Vaccination of Hepato‐HuPBL mice with the HBc/HBs peptide‐loaded pDC line elicited HBV-specific T cells in-vivo able to specifically lyse infected hepatocytes. pDCs can elicit functional virus-specific T cells in-vitro and in-vivo. This new cell-based immunotherapeutic strategy could restore functional anti‐viral immunity and clear the virus in chronic HBV patients.
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Master Thesis
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Submitted on : Thursday, December 1, 2011 - 3:22:40 PM
Last modification on : Tuesday, May 11, 2021 - 11:36:16 AM
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  • HAL Id : dumas-00647132, version 1
  • PPN : 155847643


Jérémie Martinet. Potentiel immuno-thérapeutique des pDCs dans l'hépatite B chronique. Sciences pharmaceutiques. 2011. ⟨dumas-00647132⟩



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