Immune Activation and CD8+ T-Cell Differentiation towards Senescence in HIV-1 Infection |
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| Authors: | Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno Laura Papagno |
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| Affiliation: | 1 Medical Research Council Human Immunology Unit, Institute of Molecular Medicine John Radcliffe Hospital, Oxford United Kingdom;2 Institute of Infectious and Tropical Diseases, University of Milan L. Sacco Hospital, Milan Italy;3 San Diego Veterans Affairs Research Center for AIDS and HIV Infection, University of California San Diego, La Jolla California;4 National Center of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research Epalinges Switzerland;5 Department of HIV/GUM, The Guy's Kings', and St Thomas' School of Medicine, London United Kingdom;6 Department of Virology, Royal Free and University College Medical School London United Kingdom;7 Nuffield Department of Medicine, John Radcliffe Hospital Oxford United Kingdom |
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| Abstract: | Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to elucidate the precise reasons for the onset of immunodeficiency in HIV-1 infection. Increasing evidence suggests that elevated immune activation is associated with poor outcome in HIV-1 pathogenesis. However, the basis of this association remains unclear. Through ex vivo analysis of virus-specific CD8+ T-cells and the use of an in vitro model of naïve CD8+ T-cell priming, we show that the activation level and the differentiation state of T-cells are closely related. Acute HIV-1 infection induces massive activation of CD8+ T-cells, affecting many cell populations, not only those specific for HIV-1, which results in further differentiation of these cells. HIV disease progression correlates with increased proportions of highly differentiated CD8+ T-cells, which exhibit characteristics of replicative senescence and probably indicate a decline in T-cell competence of the infected person. The differentiation of CD8+ and CD4+ T-cells towards a state of replicative senescence is a natural process. It can be driven by excessive levels of immune stimulation. This may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system. |
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