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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 3

Levels of immune activation remain low during chronic SIV infection of CD4-low sooty mangabeys.

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Levels of immune activation remain low during chronic SIV infection of C...
(A and B) Percentage of proliferating (Ki-67+) CD4+ T cells and CD8+ T cells following passage of multitropic SIV. (C) Comparison of plasma LPS levels in uninfected and chronically SIV-infected sooty mangabeys with absolute CD4+ T cell levels greater than 200 cells/mm3 blood (CD4-healthy) or less than 200 cells/mm3 blood (CD4-low; SM1, SM2, SM7, SM8, SM9 shown). Dotted line represents the average of 10 chronically SIV-infected rhesus macaques (20); Uninfected rhesus macaques have an average of 15 pg/ml LPS (20) (not shown). (D) Concentration of plasma LPS during SIV infection of SM7, SM8, and SM9. (E and F) Fold change of occludin mRNA expression in SM7, SM8, and SM9 or RMs 1–6 during acute (2–15 dpi) and chronic (184 dpi) infection or at time of necropsy. Fold change was determined relative to uninfected control animals of the same species; the fold change is considered increased or decreased when it is greater than 2 SD from the mean expression in uninfected animals (represented by the area between the dotted lines).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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