Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 Dec;76(24):13077-82.
doi: 10.1128/jvi.76.24.13077-13082.2002.

Interleukin-7 induces expression of latent human immunodeficiency virus type 1 with minimal effects on T-cell phenotype

Affiliations

Interleukin-7 induces expression of latent human immunodeficiency virus type 1 with minimal effects on T-cell phenotype

Deirdre D Scripture-Adams et al. J Virol. 2002 Dec.

Abstract

Latent human immunodeficiency virus type 1 (HIV-1) persists even in patients treated with antiretroviral therapy. New treatment strategies are therefore needed to eradicate this latent viral reservoir without reducing immune cell function. We characterize the interleukin-7 (IL-7)-induced stimulation of primary human T cells and thymocytes and demonstrate, using the SCID-hu model, that IL-7 induces substantial expression of latent HIV while having minimal effects on the cell phenotype. Thus, IL-7 is a viable candidate to activate expression of latent HIV and may facilitate immune clearance of latently infected cells.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Effect of IL-7 on human thymocytes. (A) Anti-CD3, anti-CD28 costimulated normal peripheral blood lymphocytes, either alone (right panel) or treated with N-butyrate (left panel), are shown with the cell cycle status indicated in each quadrant, as an example of the assay used in panel B, and throughout this work. DNA is depicted on the vertical axis, and RNA is depicted on the horizontal axis. The position of the vertical axis marks the division between the G1A and G1B stages of the cell cycle and is determined by the N-butyrate-treated cells, which are blocked at the G1A-to-G1B transition. Positions indicating stages in the cell cycle are illustrated in the right panel. (B) Four-color cell cycle analysis was performed on fetal thymocytes in whole-lobe thymic organ culture either alone or in the presence of IL-7 for 4 days. Three independent experiments were performed, of which one representative is shown. Top row, CD4SP and CD8SP cell populations were backgated (arrows) and analyzed for the presence of IL-7-induced changes in cell cycle progression (bottom row).
FIG. 2.
FIG. 2.
Effect of IL-7 on HIV-1 latency. (A) CD4SP thymocytes or pooled peripheral blood lymphocytes (PBL) and splenocytes were isolated from infected (HIVNL-r-HSAs or HIVJR-CSF) SCID-hu Thy/Liv implants and were cultured for three days in the presence of Protease Inhibitor, and under the following stimulation conditions: unstimulated (white), costimulated (grey), IL-7 (black), and IL-2 (striped). HIV-1 p24gag protein concentrations in the supernatants were measured to assess virus production. Each grouping of four bars represents one experiment. Unstimulated peripheral cells fell below the limit of detection (6 pg/ml). (B) Expression of virus-encoded reporter (mu CD24) indicating activation of latent virus. Mature CD4 SP thymocytes from Nl-r-HSAs infected implants were treated for 3 days without stimulation (US) or with IL-2, IL-7, or anti-CD3/CD28 costimulation as indicated. Quadrant gates were set on isotype controls.
FIG. 3.
FIG. 3.
Effect of IL-7 on surface phenotype of quiescent human lymphocytes. Total, CD45RA, or CD45RO quiescent lymphocytes were cultured in the presence or absence of IL-7. Developmental and stimulation markers were examined using flow cytometric methods. (A) Total, CD45RA, or CD45RO quiescent lymphocytes were cultured for 4 days as described previously and then analyzed for expression of CD45RA (x axis) and CD45RO (y axis) in the presence (bottom row) and absence (middle row) of IL-7, as well as on day 0 (top row). (B) CD45RA/4, CD45RA/8, CD45R0/4, and CD45R0/8 quiescent lymphocytes were isolated and cultured under the following stimulation conditions: unstimulated, IL-7, IL-2, or anti-CD3 and anti-CD28 costimulation for 3 days. Lymphocyte subsets were then analyzed for changes in expression of CCR7 (x axis) and CD62-L (y axis).
FIG. 4.
FIG. 4.
Effect of IL-7 on cell cycle status of quiescent human lymphocytes. Quiescent CD45RA/CD4, CD45RA/CD8, CD45R0/CD4, and CD45R0/CD8 lymphocytes were isolated, and cultured under the following stimulation conditions: unstimulated, IL-7, IL-2, or anti-CD3 and anti-CD28 costimulation. After 3 days, cells were stained to detect DNA (y axis) and RNA (x axis) and analyzed to determine cell cycle status. Control stimulations performed in the presence of cell cycle inhibitor (N-acetyl butyric acid) and were used to set quadrant positions (bottom row). Seven similar experiments were performed.

References

    1. Aldrovandi, G. M., G. Feuer, L. Gao, B. Jamieson, M. Kristeva, I. S. Chen, and J. A. Zack. 1993. The SCID-hu mouse as a model for HIV-1 infection. Nature 363:732-736. - PubMed
    1. Amos, C. L., A. Woetmann, M. Nielsen, C. Geisler, N. Odum, B. L. Brown, and P. R. Dobson. 1998. The role of caspase 3 and BclxL in the action of interleukin 7 (IL-7): a survival factor in activated human T cells. Cytokine 10:662-668. - PubMed
    1. Anderson, G., and E. J. Jenkinson. 1995. The role of the thymus during T-lymphocyte development in vitro. Semin. Immunol. 7:177-183. - PubMed
    1. Boise, L. H., A. J. Minn, C. H. June, T. Lindsten, and C. B. Thompson. 1995. Growth factors can enhance lymphocyte survival without committing the cell to undergo cell division. Proc. Natl. Acad. Sci. USA 92:5491-5495. - PMC - PubMed
    1. Bonyhadi, M. L., L. Rabin, S. Salimi, D. A. Brown, J. Kosek, J. M. McCune, and H. Kaneshima. 1993. HIV induces thymus depletion in vivo. Nature 363:728-732. - PubMed

Publication types

LinkOut - more resources