1. HIV preferentially infects HIV-specific CD4+ T cells.
- Author
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Douek DC, Brenchley JM, Betts MR, Ambrozak DR, Hill BJ, Okamoto Y, Casazza JP, Kuruppu J, Kunstman K, Wolinsky S, Grossman Z, Dybul M, Oxenius A, Price DA, Connors M, and Koup RA
- Subjects
- Anti-HIV Agents administration & dosage, Anti-HIV Agents therapeutic use, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Cell Division, Cells, Cultured, DNA, Viral blood, HIV genetics, HIV isolation & purification, HIV Infections drug therapy, HIV Infections immunology, Humans, Immunologic Memory, Interferon-gamma metabolism, Male, Organ Specificity, Polymerase Chain Reaction, Viral Load, CD4-Positive T-Lymphocytes virology, HIV physiology, HIV Infections virology
- Abstract
HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. 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 affected. 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 replication. 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.
- Published
- 2002
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