Chloroquine enhances human CD8<b>+</b> T cell responses against soluble antigens in vivo

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  • Daniele Accapezzato
    1Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna
  • Vincenzo Visco
    2Dipartimento di Medicina Sperimentale e Patologia, Università degli Studi di Roma “La Sapienza,” 00161 Rome, Italy
  • Vittorio Francavilla
    1Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna
  • Caroline Molette
    1Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna
  • Tiziana Donato
    1Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna
  • Marino Paroli
    1Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna
  • Mario U. Mondelli
    4Laboratori Sperimentali di Ricerca, Area Infettivologica e Dipartimento di Malattie Infettive, IRCCS Policlinico San Matteo and Università degli Studi di Pavia, 27100 Pavia, Italy
  • Margherita Doria
    5Divisione di Immunologia e Malattie Infettive, Ospedale Pediatrico “Bambino Gesù,” 00133 Rome, Italy
  • Maria Rosaria Torrisi
    2Dipartimento di Medicina Sperimentale e Patologia, Università degli Studi di Roma “La Sapienza,” 00161 Rome, Italy
  • Vincenzo Barnaba
    1Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna

抄録

<jats:p>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 cross-presentation 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 chloroquine-treated 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.</jats:p>

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