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Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells
Jeffrey M. Milush, … , Guido Silvestri, Donald L. Sodora
Jeffrey M. Milush, … , Guido Silvestri, Donald L. Sodora
Published February 7, 2011
Citation Information: J Clin Invest. 2011;121(3):1102-1110. https://doi.org/10.1172/JCI44876.
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Research Article Virology

Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells

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Abstract

SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3+CD4–CD8– T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4+ T cells to SIV-negative animals resulted in rapid loss of CD4+ T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell–like helper functions upon SIV-induced CD4+ T cell depletion in this species.

Authors

Jeffrey M. Milush, Kiran D. Mir, Vasudha Sundaravaradan, Shari N. Gordon, Jessica Engram, Christopher A. Cano, Jacqueline D. Reeves, Elizabeth Anton, Eduardo O’Neill, Eboneé Butler, Kathy Hancock, Kelly S. Cole, Jason M. Brenchley, James G. Else, Guido Silvestri, Donald L. Sodora

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Figure 1

Passage of multitropic SIV results in dramatic CD4+ T cell decline in multiple tissue compartments.

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Passage of multitropic SIV results in dramatic CD4+ T cell decline in mu...
(A) Absolute numbers of peripheral blood CD4+ T cells prior to and following passage of multitropic SIV from 1 CD4-low SIV+ mangabey to SM7, SM8, and SM9. (B) Plasma viral loads following passage as measured by the number of copies of gag RNA per ml of plasma. (C) Absolute numbers of peripheral blood CD8+ T cells following SIV infection. (D) Representative flow data showing the percentage of CD4+, CD8+, and DN T cells (indicated by boxes in lower right, upper left, and lower left sections of flow plots, respectively) in BAL, rectal biopsy (RB), and LN samples at –60, 14, and 180 dpi in SM7. Events shown were gated through live/dead and CD3+ gates.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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