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    Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4(+) T Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative Responses.

    246945.pdf (1.083Mb)
    Access Status
    Open access
    Authors
    Tanaskovic, S.
    Price, Patricia
    French, M.
    Fernandez, S.
    Date
    2016
    Type
    Journal Article
    
    Metadata
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    Citation
    Tanaskovic, S. and Price, P. and French, M. and Fernandez, S. 2016. Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4(+) T Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative Responses. AIDS Research and Human Retroviruses. 33 (2): pp. 101-109.
    Source Title
    AIDS Research and Human Retroviruses
    DOI
    10.1089/AID.2015.0327
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/47208
    Collection
    • Curtin Research Publications
    Abstract

    HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4(+) T cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules, following anti-CD3 stimulation, in HIV patients with persistent CD4(+) T cell deficiency on ART. Aviremic HIV patients with nadir CD4(+) T cell counts <100 cells/µL and who had received ART for a median time of 7 (range 1-11) years were categorized into those achieving low (<350 cells/µL; n?=?13) or normal (>500 cells/µL; n?=?20) CD4(+) T cell counts. Ten healthy controls were also recruited. CD4(+) T cell proliferation (Ki67) and upregulation of costimulatory molecules (CD27 and CD28) after anti-CD3 stimulation were assessed by flow cytometry. Results were related to proportions of CD4(+) T cells expressing markers of T cell senescence (CD57), activation (HLA-DR), and apoptotic potential (Fas). Expression of CD27 and/or CD28 on uncultured CD4(+) T cells was similar in patients with normal CD4(+) T cell counts and healthy controls, but lower in patients with low CD4(+) T cell counts. Proportions of CD4(+) T cells expressing CD27 and/or CD28 correlated inversely with CD4(+) T cell expression of CD57, HLA-DR, and Fas. After anti-CD3 stimulation, induction of CD27(hi)CD28(hi) expression was independent of CD4(+) T cell counts, but lower in HIV patients than in healthy controls. Induction of CD27(hi)CD28(hi) expression correlated with induction of Ki67 expression in total, naïve, and CD31(+) naïve CD4(+) T cells from patients. In HIV patients responding to ART, impaired induction of CD27 and CD28 on CD4(+) T cells after stimulation with anti-CD3 is associated with poor proliferative responses as well as greater CD4(+) T cell activation and immunosenescence.

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