HIV preferentially infects HIV-specific CD4+ T cells (original) (raw)

• Letter
• Published: 02 May 2002
• Jason M. Brenchley1 na1,
• Michael R. Betts1,
• David R. Ambrozak1,
• Brenna J. Hill1,
• Yukari Okamoto1,
• Joseph P. Casazza4,
• Janaki Kuruppu1,
• Kevin Kunstman5,
• Steven Wolinsky5,
• Zvi Grossman6,7,
• Mark Dybul2,
• Annette Oxenius8 na1,
• David A. Price8 na1,
• Mark Connors2 &
• …
• Richard A. Koup1

Nature volume 417, pages 95–98 (2002)Cite this article

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Abstract

HIV infection is associated with the progressive loss of CD4+ T cells through their destruction or decreased production1,2. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4+ T cells are preferentially affected3,4,5. Here we show that HIV-specific memory CD4+ T cells in infected individuals contain more HIV viral DNA than other memory CD4+ T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4+ T cells increases to a greater extent than in memory CD4+ T cells of other specificities. These findings show that HIV-specific CD4+ T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4+ T-cell responses, and consequently the loss of immunological control of HIV replication6. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.

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Acknowledgements

We thank the patients and staff at UTSW Medical Center and the NIH for their cooperation, and M. Roederer and J. Mascola for their help. This work was supported by the UK Medical Research Council (D.A.P.), the Wellcome Trust, and the National Institutes of Health (S.W.).

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Author notes

1. Daniel C. Douek, Jason M. Brenchley, Annette Oxenius and David A. Price: These authors contributed equally to this work

Authors and Affiliations

1. Vaccine Research Center, NIAID, NIH, Maryland, 20892, USA
   Daniel C. Douek, Jason M. Brenchley, Michael R. Betts, David R. Ambrozak, Brenna J. Hill, Yukari Okamoto, Janaki Kuruppu & Richard A. Koup
2. Laboratory of Immunoregulation, NIAID, NIH, Maryland, 20892, USA
   Mark Dybul & Mark Connors
3. Department of Experimental Transplantation and Immunology, Medicine Branch, NCI, NIH, Maryland, 20892, USA
   Daniel C. Douek
4. Department of Medicine, University of Texas Southwestern Medical Center, Texas, Dallas, 75390, USA
   Joseph P. Casazza
5. Department of Infectious Diseases, Northwestern University Medical School, Illinois, Chicago, 60611, USA
   Kevin Kunstman & Steven Wolinsky
6. Laboratory of Immunology, NIAID, NIH, Maryland, USA
   Zvi Grossman
7. Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv, 69978, Israel
   Zvi Grossman
8. Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, UK
   Annette Oxenius & David A. Price

Authors

1. Daniel C. Douek
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2. Jason M. Brenchley
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3. Michael R. Betts
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4. David R. Ambrozak
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5. Brenna J. Hill
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6. Yukari Okamoto
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7. Joseph P. Casazza
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8. Janaki Kuruppu
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9. Kevin Kunstman
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10. Steven Wolinsky
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11. Zvi Grossman
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12. Mark Dybul
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13. Annette Oxenius
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14. David A. Price
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15. Mark Connors
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16. Richard A. Koup
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Correspondence toDaniel C. Douek.

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Douek, D., Brenchley, J., Betts, M. et al. HIV preferentially infects HIV-specific CD4+ T cells.Nature 417, 95–98 (2002). https://doi.org/10.1038/417095a

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• Received: 05 November 2001
• Accepted: 25 February 2002
• Issue Date: 02 May 2002
• DOI: https://doi.org/10.1038/417095a

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