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Loss of DNAM-1 contributes to CD8+ T-cell exhaustion in chronic HIV-1 infection

  1. Marina Cella1,
  2. Rachel Presti1,
  3. William Vermi2,
  4. Kerry Lavender3,
  5. Emma Turnbull3,
  6. Christina Ochsenbauer-Jambor4,
  7. John C. Kappes4,
  8. Guido Ferrari5,
  9. Lisa Kessels6,
  10. Ian Williams7,
  11. Andrew J. McMichael8,
  12. Barton F. Haynes5,
  13. Persephone Borrow3,
  14. Marco Colonna1,*

Article first published online: 3 MAR 2010

DOI: 10.1002/eji.200940234

Issue

European Journal of Immunology

European Journal of Immunology

Volume 40, Issue 4, pages 949–954, April 2010

Additional Information

How to Cite

Cella, M., Presti, R., Vermi, W., Lavender, K., Turnbull, E., Ochsenbauer-Jambor, C., Kappes, J. C., Ferrari, G., Kessels, L., Williams, I., McMichael, A. J., Haynes, B. F., Borrow, P. and Colonna, M. (2010), Loss of DNAM-1 contributes to CD8+ T-cell exhaustion in chronic HIV-1 infection. Eur. J. Immunol., 40: 949–954. doi: 10.1002/eji.200940234

Author Information

  1. 1

    Department of Pathology, Washington University School of Medicine, St. Louis, MO, USA

  2. 2

    Department of Pathology I, Spedali Civili, University of Brescia, Brescia, Italy

  3. 3

    The Jenner Institute, University of Oxford, Compton, UK

  4. 4

    University of Alabama at Birmingham, Birmingham, AL, USA

  5. 5

    Duke University Medical Center, Durham, NC, USA

  6. 6

    AIDS Clinical Trial Unit, Washington University School of Medicine, St. Louis, MO, USA

  7. 7

    Centre for Sexual Health & HIV Research, Mortimer Market Centre, London, UK

  8. 8

    Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

*Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Fax: +1-314-3624096

Publication History

  1. Issue published online: 14 APR 2010
  2. Article first published online: 3 MAR 2010
  3. Manuscript Accepted: 3 MAR 2010
  4. Manuscript Revised: 18 JAN 2010
  5. Manuscript Received: 9 DEC 2009

Funded by

  • NIAID Center for HIV/AIDS Vaccine Immunology. Grant Numbers: A1067854, JDRF♯ 24–2008–938

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Keywords:

  • Co-stimulation;
  • Exhaustion;
  • HIV-1

Abstract

The hallmark of chronic viral infections is a progressive exhaustion of antigen-specific CD8+ T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8+ T cells that makes them dysfunctional. Here, we show that during human chronic HIV-1 infection, a CD8+ T-cell positive costimulatory pathway mediated by DNAX-activating molecule-1 is also disrupted. Thus, DNAX-activating molecule-1 downregulation on CD8+ T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection.

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