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HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression

Abstract

The role of HIV-1-specific CD4+ T-cell responses in controlling HIV-1 infection remains unclear. Previous work has suggested that such cells are eliminated in the early stages of infection in most subjects, and thus cannot substantially contribute to host defense against HIV-1. Here, using flow cytometric detection of antigen-induced intracellular cytokines, we show that significant frequencies of gag specific, T-helper-1 CD4+ memory T cells are detectable in most subjects with active/progressive HIV-1 infection (median frequency, 0.12% of memory subset; range, 0–0.66%). Median frequencies of these cells were considerably higher in nonprogressive HIV-1 disease (0.40%), but there was substantial overlap between the two groups (range of nonprogressors, 0.10–1.7%). Continuous HIV-1 suppression with anti-retroviral therapy was associated with a time-dependent reduction in median frequencies of gag-specific CD4+ memory T cells: 0.08% in subjects treated for 4–24 weeks, and 0.03% in subjects treated for 47–112 weeks. Thus, functional HIV-1-specific CD4+ T cells are commonly available for support of anti-HIV-1 effector responses in active disease, but their decline with anti-retroviral therapy indicates that immunologic participation in long-term HIV-1 control will probably require effective vaccination strategies.

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Figure 1: Detection and characterization of HIV-1 specific CD4+ T cells in HIV-1-positive subjects with long-term nonprogressive disease.
Figure 2: Quantification of gag-p55- and CMV-specific CD4+ memory T-cell.
Figure 3: Analysis of gag-p55- and CMV-specific CD4+ memory T cells.

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Acknowledgements

We thank D. Douek and R. McFarland for critical review of the manuscript, D. Ambrosak and Fred Scott for technical assistance, W. Frawley for statistical analysis, R. Moss, P. Valenzuela, and G. Naciemento for provision of antigen preparations, B. Dawson for viral load determinations, and R. Barber and P. Keiser for assistance with subject recruitment. This work was supported by NIH grants AI31545 (L.J.P) and AI35522 (R.A.K), a grant from the Texas Higher Education Coordinating Board (L.J.P.), and the UT Southwestern AIDS Clinical Research Fund (D.M.P.). R.A.K. is an Elizabeth Glaser Scientist of the Pediatric AIDS Foundation.

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Pitcher, C., Quittner, C., Peterson, D. et al. HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression . Nat Med 5, 518–525 (1999). https://doi.org/10.1038/8400

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