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

@article{citeulike:3361849, 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 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. 10.1084/jem.20051106}, author = {Accapezzato, Daniele and Visco, Vincenzo and Francavilla, Vittorio and Molette, Caroline and Donato, Tiziana and Paroli, Marino and Mondelli, Mario U. and Doria, Margherita and Torrisi, Maria R. and Barnaba, Vincenzo}, citeulike-article-id = {3361849}, citeulike-linkout-0 = {http://dx.doi.org/10.1084/jem.20051106}, citeulike-linkout-1 = {http://www.jem.org/cgi/content/abstract/202/6/817}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16157687}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16157687}, day = {19}, doi = {10.1084/jem.20051106}, journal = {J. Exp. Med.}, keywords = {antigen-processing, cd8, chloroquine, mhc-class-ii}, month = {September}, number = {6}, pages = {817--828}, posted-at = {2008-10-01 12:24:18}, priority = {2}, title = {Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo}, url = {http://dx.doi.org/10.1084/jem.20051106}, volume = {202}, year = {2005} }

TY - JOUR ID - citeulike:3361849 L3 - citeulike-article-id:3361849 N2 - 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. 10.1084/jem.20051106 IS - 6 JF - J. Exp. Med. EP - 828 TI - Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo VL - 202 SP - 817 KW - antigen-processing KW - cd8 KW - chloroquine KW - mhc-class-ii AU - Accapezzato, Daniele AU - Visco, Vincenzo AU - Francavilla, Vittorio AU - Molette, Caroline AU - Donato, Tiziana AU - Paroli, Marino AU - Mondelli, Mario AU - Doria, Margherita AU - Torrisi, Maria AU - Barnaba, Vincenzo PY - 2005/09/19/ UR - http://dx.doi.org/10.1084/jem.20051106 ER -