Immune Activation and CD+ T-Cell Differentiation towards Senescence in HIV-1 Infection.

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. [ABSTRACT FROM AUTHOR]