Mini ReviewAccelerated immune senescence and HIV-1 infection
Section snippets
The course of HIV-1 infection
Over the past 40 years, from isolated case reports, the scale of the HIV-1 epidemic has become a global pandemic, and HIV-1 has become the most extensively studied pathogen in history. The clinical course of HIV-1 infection can be divided into three distinct stages (Fig. 1). The acute HIV-1 infection stage is characterised by widespread viral dissemination, which is generally halted within 1–4 weeks with the induction of host cellular immune response. However, while the immune system is able to
Immune activation and decline of immunity in HIV-1 infection
As HIV-1 persists in its host, the immune system continues to be challenged overtime, and immune activation and inflammation become generalized. This has long been characterized, with the observation of elevated levels of activated CD4+ and CD8+ T-cells, high CD8+ T-cell counts, increased T-cell apoptosis as well as increased levels inflammatory cytokines (like IL-6, TNF-α and IL-1β). In recent years, a consensus has been reached in the sense that this phenomenon of chronic immune activation
Exhaustion of HIV-specific CD8+ T-cell clonal populations
Accumulating evidence suggests that the cells of the immune system may have a limited replicative lifespan and can reach a state of replicative senescence in vivo (Pawelec et al., 1999). The occurrence of replicative senescence is primarily related to the number of cell divisions. For viral infections where the pathogen is eliminated by the cellular immune response during primary infection, the host is left with a population of memory cells, that should retain a good replicative potential in
Systemic exhaustion
Nonetheless, it is important to appreciate that activation driven immune exhaustion in HIV-1 infection may go far beyond the simple loss of virus specific CD8+ T-cell clones. HIV-1 infected donors are characterized by increasing proportions of highly differentiated CD8+ or CD4+ T-cells (CD27−/CD28−) over the different stages of the HIV-1 infection course ((Papagno et al., 2004) and VA, unpublished data) (Fig. 3). In order to gain further insight into the significance of increased T-cell
Concluding remarks
Loss of HIV replication control and progression towards HIV disease may the consequence of immune resources exhaustion due to persistent immune activation. This may happen at two levels: clonal exhaustion of HIV-specific CD8+ T-cells important to control HIV replication and systemic exhaustion of primary resources resulting in the decline of T-cell renewal capacities and a general ageing of the lymphocyte population, alike the natural process of immunosenescence taking place with age.
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