Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo

Daniele Accapezzato, Vincenzo Visco, Vittorio Francavilla, Caroline Molette, Tiziana Donato, Marino Paroli, Mario U. Mondelli, Margherita Doria, Maria Rosaria Torrisi, Vincenzo Barnaba

Research output: Contribution to journalArticle

Abstract

The presentation of exogenous protein antigens in a major histocompatibility complex class I-restricted fashion to CD8+ T cells is called cross-presentation. We demonstrate that crosspresentation of soluble viral antigens (derived from hepatitis C virus [HCV], hepatitis B virus [HBV], or human immunodeficiency virus) to specific CD8+ T cell clones is dramatically improved when antigen-presenting dendritic cells (DCs) are pulsed with the antigen in the presence of chloroquine or ammonium chloride, which reduce acidification of the endocytic system. The export of soluble antigen into the cytosol is considerably higher in chloroquinetreated than in untreated DCs, as detected by confocal microscopy of cultured cells and Western blot analysis comparing endocytic and cytosolic fractions. To pursue our findings in an in vivo setting, we boosted groups of HBV vaccine responder individuals with a further dose of hepatitis B envelope protein vaccine with or without a single dose of chloroquine. Although all individuals showed a boost in antibody titers to HBV, six of nine individuals who were administered chloroquine showed a substantial CD8+ T cell response to HBV antigen, whereas zero of eight without chloroquine lacked a CD8 response. Our results suggest that chloroquine treatment improves CD8 immunity during vaccination. JEM

Original languageEnglish
Pages (from-to)817-828
Number of pages12
JournalJournal of Experimental Medicine
Volume202
Issue number6
DOIs
Publication statusPublished - Sep 19 2005

ASJC Scopus subject areas

  • Immunology

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    Accapezzato, D., Visco, V., Francavilla, V., Molette, C., Donato, T., Paroli, M., Mondelli, M. U., Doria, M., Torrisi, M. R., & Barnaba, V. (2005). Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo. Journal of Experimental Medicine, 202(6), 817-828. https://doi.org/10.1084/jem.20051106