B7‐H1 up‐regulation impairs myeloid DC and correlates with disease progression in chronic HIV‐1 infection

B7‐H1 up‐regulation impairs myeloid DC and correlates with disease progression in chronic... Impaired myeloid dendritic cells (mDC) fail to elicit host antiviral immune responses, leading to disease progression in HIV‐1 infection. However, mechanisms underlying mDC suppression remain elusive. In this study, we found that the T‐cell co‐stimulatory molecule programmed death‐1 ligand‐1 (B7‐H1) is significantly up‐regulated on peripheral mDC in HIV‐1‐infected typical progressors and AIDS patients, but is maintained at a relatively low level in long‐term non‐progressors. Successful immune reconstitution after highly active antiretroviral therapy, indicated by full suppression of HIV‐1 replication and substantial increases of CD4 T‐cell counts, correlated with a decrease in B7‐H1 expression. Importantly, we also found that X4 HIV‐1 isolates directly induced B7‐H1 expression on mDC in vitro, while adding antiviral agents hampered this B7‐H1 up‐regulation. Blockade of B7‐H1 in vitro strongly enhanced mDC‐mediated allostimulatory capacity and IL‐12 production. In contrast, B7‐H1 ligation with soluble programmed death‐1 (PD‐1) reduced mDC maturation and IL‐12 production but increased mDC apoptosis and IL‐10 production. Thus, B7‐H1 up‐regulation may inhibit mDC‐mediated immune response, thereby facilitating viral persistence and disease progression in HIV‐1‐infected patients. This study provides new evidence that B7‐H1 inhibitory signaling may reversely mediate functional impairment of mDC in HIV‐1 infection, which further supports the notion that B7‐H1 blockade represents a novel therapeutic approach to this disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Immunology Wiley

B7‐H1 up‐regulation impairs myeloid DC and correlates with disease progression in chronic HIV‐1 infection

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
Copyright © 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
0014-2980
eISSN
1521-4141
D.O.I.
10.1002/eji.200838285
Publisher site
See Article on Publisher Site

Abstract

Impaired myeloid dendritic cells (mDC) fail to elicit host antiviral immune responses, leading to disease progression in HIV‐1 infection. However, mechanisms underlying mDC suppression remain elusive. In this study, we found that the T‐cell co‐stimulatory molecule programmed death‐1 ligand‐1 (B7‐H1) is significantly up‐regulated on peripheral mDC in HIV‐1‐infected typical progressors and AIDS patients, but is maintained at a relatively low level in long‐term non‐progressors. Successful immune reconstitution after highly active antiretroviral therapy, indicated by full suppression of HIV‐1 replication and substantial increases of CD4 T‐cell counts, correlated with a decrease in B7‐H1 expression. Importantly, we also found that X4 HIV‐1 isolates directly induced B7‐H1 expression on mDC in vitro, while adding antiviral agents hampered this B7‐H1 up‐regulation. Blockade of B7‐H1 in vitro strongly enhanced mDC‐mediated allostimulatory capacity and IL‐12 production. In contrast, B7‐H1 ligation with soluble programmed death‐1 (PD‐1) reduced mDC maturation and IL‐12 production but increased mDC apoptosis and IL‐10 production. Thus, B7‐H1 up‐regulation may inhibit mDC‐mediated immune response, thereby facilitating viral persistence and disease progression in HIV‐1‐infected patients. This study provides new evidence that B7‐H1 inhibitory signaling may reversely mediate functional impairment of mDC in HIV‐1 infection, which further supports the notion that B7‐H1 blockade represents a novel therapeutic approach to this disease.

Journal

European Journal of ImmunologyWiley

Published: Nov 1, 2008

References

  • IPC: professional type 1 interferon‐producing cells and plasmacytoid dendritic cell precursors
    Liu, Liu
  • Myeloid and plasmacytoid dendritic cells transfer HIV‐1 preferentially to antigen‐specific CD4 + T cells
    Lore, Lore; Smed‐Sorensen, Smed‐Sorensen; Vasudevan, Vasudevan; Mascola, Mascola; Koup, Koup
  • PD‐1 is a regulator of virus‐specific CD8 + T cell survival in HIV infection
    Petrovas, Petrovas; Casazza, Casazza; Brenchley, Brenchley; Price, Price; Gostick, Gostick; Adams, Adams; Precopio, Precopio
  • B7‐H1 expression is upregulated in peripheral blood CD14 + monocytes of patients with chronic hepatitis B virus infection, which correlates with higher serum IL‐10 levels
    Geng, Geng; Jiang, Jiang; Fang, Fang; Dong, Dong; Xie, Xie; Chen, Chen; Shen, Shen; Zheng, Zheng
  • Expression of programmed‐death receptor ligands 1 and 2 may contribute to the poor stimulatory potential of murine immature dendritic cells
    Chen, Chen; Qu, Qu; Huang, Huang; Zhu, Zhu; Ge, Ge; Wang, Wang; Zhang, Zhang
  • Resolution of a chronic viral infection after interleukin‐10 receptor blockade
    Ejrnaes, Ejrnaes; Filippi, Filippi; Martinic, Martinic; Ling, Ling; Togher, Togher; Crotty, Crotty; von Herrath, von Herrath
  • Low interleukin‐10 production is associated with diabetes in HIV‐infected patients undergoing antiviral therapy
    Trabattoni, Trabattoni; Schenal, Schenal; Cesari, Cesari; Castelletti, Castelletti; Pacei, Pacei; Goldberg, Goldberg; Gori, Gori; Clerici, Clerici

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