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- Title
Immune Activation and CD8<sup>+</sup> T-Cell Differentiation towards Senescence in HIV-1 Infection.
- Authors
Papagno, Laura; Spina, Celsa A; Marchant, Arnaud; Salio, Mariolina; Rufer, Nathalie; Little, Susan; Dong, Tao; Chesney, Gillian; Waters, Anele; Easterbrook, Philippa; Dunbar, P. Rod; Shepherd, Dawn; Cerundolo, Vincenzo; Emery, Vincent; Griffiths, Paul; Conlon, Christopher; McMichael, Andrew J; Richman, Douglas D; Rowland-Jones, Sarah L; Appay, Victor
- 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. HIV-1 infection induces activation and differentiation of CD8+ T-cells, resulting in replicative senescence. This may be part of the mechanism through which HIV-1 exhausts the capacity of the immune system.
- Publication
PLoS Biology, 2004, Vol 2, Issue 2, p1
- ISSN
1544-9173
- Publication type
Academic Journal
- DOI
10.1371/journal.pbio.0020020