Mobilizing monocytes to cross-present circulating viral antigen in chronic infection

Selection of antigens for therapeutic vaccination against chronic viral infections is complicated by pathogen genetic variations. We tested whether antigens present during persistent viral infections could provide a personalized antigenic reservoir for therapeutic T cell expansion in humans. We focu...

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Bibliographic Details
Published in:The Journal of clinical investigation 2013-09, Vol.123 (9), p.3766-3776
Main Authors: Gehring, Adam J, Haniffa, Muzlifah, Kennedy, Patrick T, Ho, Zi Zong, Boni, Carolina, Shin, Amanda, Banu, Nasirah, Chia, Adeline, Lim, Seng Gee, Ferrari, Carlo, Ginhoux, Florent, Bertoletti, Antonio
Format: Article
Language:English
Subjects:
B-Lymphocytes - immunology
B-Lymphocytes - virology
Biomedical research
Cell Proliferation
Cells, Cultured
Coculture Techniques
Cross-Priming
Dendritic Cells - immunology
Dendritic Cells - virology
Health aspects
Hepatitis B Surface Antigens - blood
Hepatitis B Surface Antigens - immunology
Hepatitis B virus
Hepatitis B virus - immunology
Hepatitis B, Chronic - blood
Hepatitis B, Chronic - immunology
Humans
Immune system
Immunology
Infection
Lymphocytes
Microscopy
Monocytes - immunology
Monocytes - virology
Patients
Peptides
Studies
T cells
T-Lymphocytes - immunology
T-Lymphocytes - virology
Vaccines
Viral antigens
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Summary:Selection of antigens for therapeutic vaccination against chronic viral infections is complicated by pathogen genetic variations. We tested whether antigens present during persistent viral infections could provide a personalized antigenic reservoir for therapeutic T cell expansion in humans. We focused our study on the HBV surface antigen (HBsAg), which is present in microgram quantities in the serum of chronic HBV patients. We demonstrated by quantitative fluorescent microscopy that, out of 6 professional APC populations in the circulation, only CD14 monocytes (MNs) retained an HBsAg depot. Using TCR-redirected CD8+ T cells specific for MHC-I-restricted HBV epitopes, we showed that, despite being constantly exposed to antigen, ex vivo-isolated APCs did not constitutively activate HBV-specific CD8+ T cells. However, differentiation of HBsAg+ CD14 MNs from chronic patients to MN-derived DCs (moDCs) induced cross-presentation of the intracellular reservoir of viral antigen. We exploited this mechanism to cross-present circulating viral antigen and showed that moDCs from chronically infected patients stimulated expansion of autologous HBV-specific T cells. Thus, these data demonstrate that circulating viral antigen produced during chronic infection can serve as a personalized antigenic reservoir to activate virus-specific T cells.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci66043