Clinical immunology

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

  1. Xicheng Wang1,†,
  2. Zheng Zhang2,†,
  3. Shuye Zhang2,
  4. Junliang Fu2,
  5. Jinxia Yao2,
  6. Yanmei Jiao1,
  7. Hao Wu1,*,
  8. Fu-Sheng Wang2,*

Article first published online: 16 OCT 2008

DOI: 10.1002/eji.200838285

Issue

European Journal of Immunology

European Journal of Immunology

Volume 38, Issue 11, pages 3226–3236, November 2008

Additional Information

How to Cite

Wang, X., Zhang, Z., Zhang, S., Fu, J., Yao, J., Jiao, Y., Wu, H. and Wang, F.-S. (2008), B7-H1 up-regulation impairs myeloid DC and correlates with disease progression in chronic HIV-1 infection. Eur. J. Immunol., 38: 3226–3236. doi: 10.1002/eji.200838285

Author Information

  1. 1

    Department of Infectious Diseases, Beijing You-An Hospital Affiliated to Capital Medical University, China

  2. 2

    Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, China

  1. †

    These authors contributed equally to this study.

*Department of Infectious Diseases, Beijing You-an Hospital Affiliated to Capital Medical University, Beijing 100069, China Fax: +86-10-6329 7701

Publication History

  1. Issue published online: 7 NOV 2008
  2. Article first published online: 16 OCT 2008
  3. Manuscript Accepted: 6 AUG 2008
  4. Manuscript Revised: 31 JUL 2008
  5. Manuscript Received: 25 FEB 2008

Funded by

  • National Key Basic Research Program of China. Grant Numbers: 2006CB504205, 2006CB504201, 2006AA02Z411
  • National Outstanding Youth Foundation of China. Grant Number: 30525042

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Keywords:

  • B7-H1;
  • Co-stimulation;
  • HIV;
  • Myeloid dendritic cells;
  • PD-1

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.

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