Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo.
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.
Accapezzato
Daniele
D
Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna, Università degli Studi di Roma La Sapienza, Rome, Italy.
Visco
Vincenzo
V
Francavilla
Vittorio
V
Molette
Caroline
C
Donato
Tiziana
T
Paroli
Marino
M
Mondelli
Mario U
MU
Doria
Margherita
M
Torrisi
Maria Rosaria
MR
Barnaba
Vincenzo
V
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D000962:Antimalarials / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D045142:Cross-Priming / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D018613:Microscopy, Confocal; D012995:Solubility; D015854:Up-Regulation / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000276:immunology / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000276:Adjuvants, Immunologic; D000941:Antigens; D000962:Antimalarials; D002738:Chloroquine; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases