• Retrovirology · Jan 2015

    Increased susceptibility of CD4+ T cells from elderly individuals to HIV-1 infection and apoptosis is associated with reduced CD4 and enhanced CXCR4 and FAS surface expression levels.

    • Anke Heigele, Simone Joas, Kerstin Regensburger, and Frank Kirchhoff.
    • Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. anke.heigele@uni-ulm.de.
    • Retrovirology. 2015 Jan 1; 12: 86.

    BackgroundElderly HIV-1 infected individuals progress to AIDS more frequently and rapidly than people becoming infected at a young age. To identify possible reasons for these differences in clinical progression, we performed comprehensive phenotypic analyses of CD4+ T cells from uninfected young and elderly individuals, and examined their susceptibility to HIV-1 infection and programmed death.ResultsPeripheral blood mononuclear cells (PBMCs) from older people contain an increased percentage of central memory and Th17 CD4+ T cells that are main target cells of HIV-1 and strongly reduced proportions of naïve T cells that are poorly susceptible to HIV-1. Unstimulated T cells from elderly individuals expressed higher levels of activation markers, death receptors, and the viral CXCR4 co-receptor than those from young individuals but responded poorly to stimulation. CD4+ T cells from older individuals were highly susceptible to CXCR4- and CCR5-tropic HIV-1 infection but produced significantly lower quantities of infectious virus than cells from young individuals because they were highly prone to apoptosis and thus presumably had a very short life span. The increased susceptibility of T cells from the elderly to HIV-1 infection correlated directly with CXCR4 and inversely with CD4 expression. The levels of apoptosis correlated with the cell surface expression of FAS but not with the expression of programmed death receptor 1 (PD1) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).ConclusionsIncreased levels of activated and highly susceptible HIV-1 target cells, reduced CD4 and enhanced CXCR4 cell surface expression, together with the high susceptibility to FAS-induced programmed cell death may contribute to the rapid CD4+ T cell depletion and accelerated clinical course of infection in elderly HIV-1-infected individuals.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…