Plasmacytoid dendritic cells induce efficient stimulation of anti-viral immunity in the context of chronic HBV infection.
Summary of "Plasmacytoid dendritic cells induce efficient stimulation of anti-viral immunity in the context of chronic HBV infection."
The immune control of HBV infection is essential for viral clearance. Therefore, restoring functional anti-HBV immunity is a promising immunotherapeutic approach to treatment of chronic infection. Plasmacytoid dendritic cells (pDC) play a crucial role in triggering anti-viral immunity through their ability to capture and process viral antigens and subsequently induce adaptive immune responses. In this article, we investigated pDCs potential to trigger anti-viral cellular immunity against HBV. We used a HLA-A*0201(+) pDC line loaded with HLA-A*0201-restricted peptides derived from HBc/HBs antigens to amplify specific CD8 T-cells ex vivo from chronic HBV patients and established an Hepato-HuPBL mouse model to address the therapeutic potential of the strategy in vivo. Stimulation of PBMC or liver-infiltrating lymphocytes (LIL) from HLA-A*0201(+) chronic HBV patients by HBc peptide-loaded pDCs elicited up to 23.1% and 76.1% HBV-specific CD8 T-cells in 45.8% of cases. The specific T-cells from the "responder" group secreted IFNγ, expressed CD107 upon restimulation and efficiently lysed HBV antigen-expressing hepatocytes. Circulating HBeAg was found to distinguish the group of patients not responding to the pDC stimulation. The therapeutic efficacy of the pDC-vaccine was evaluated in immunodeficient NOD-SCIDβ(2) m(-/-) mice reconstituted with HBV patients' PBMC and xenotransplanted with human HBV-transfected hepatocytes. Vaccination of Hepato-HuPBL mice with the HBc/HBs peptide-loaded pDCs elicited HBV-specific T cells able to specifically lyse the transfected hepatocytes and reduce the systemic viral load.
CONCLUSION:
pDCs loaded with HBV-derived peptides can elicit functional virus-specific T-cells. HBeAg appears to be critical in determining the outcome of immunotherapies in chronic HBV patients. A pDC-based immunotherapeutic approach could be of interest in attempts to restore functional anti-viral immunity, which is critical for the control of the virus in chronic HBV patients. (HEPATOLOGY 2012.).
Affiliation
EFS Rhone-Alpes, R&D Laboratory, La Tronche, F-38701 France; University Joseph Fourier, Grenoble, F-38041 France; INSERM, U823, Immunobiology & Immunotherapy of Cancers, La Tronche, F-38706 France; CHU Grenoble, Michallon Hospital, Cancerology and Biother
Journal Details
This article was published in the following journal.
Name: Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22707082
- DOI: http://dx.doi.org/10.1002/hep.25879
Medical and Biotech [MESH] Definitions
Dendritic Cells, Follicular
Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.
Langerhans Cells
Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS.
Interleukin-12
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
Antigen-presenting Cells
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Plaque Assay
Method for measuring viral infectivity and multiplication in cultured cells. Clear lysed areas or plaques develop as the viral particles are released from the infected cells during incubation. With some viruses, the cells are killed by a cytopathic effect; with others, the infected cells are not killed but can be detected by their hemadsorptive ability. Sometimes the plaque cells contain viral antigens which can be measured by immunofluorescence.
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