CD4+ T-cell depletion in HIV infection: are we closer to understanding the cause?

Grossman, Zvi; Meier-Schellersheim, Martin; Sousa, Ana E.; Victorino, Rui M. M.; Paul, William E.

http://hdl.handle.net/10451/20111

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Authors

Grossman, Zvi

Meier-Schellersheim, Martin

Sousa, Ana E.

Victorino, Rui M. M.

Paul, William E.

Abstract(s)

The cause of the progressive depletion of CD4+ T cells in HIV-infected people is one of the most fundamental and controversial issues in AIDS research. HIV infects and kills CD4+ T cells. The infection results in high T-cell activation and turnover. An immediately intuitive assumption is that HIV-mediated destruction of CD4+ cells directly reduces the number of these cells and that the high turnover rates of T cells and the slow progression to AIDS reflect a long, but eventually lost struggle of the immune system to replace killed cells in its effort to maintain T-cell homeostasis1–4. However, HIV mainly infects activated CD4+ cells, and activated cells normally follow different dynamics than cells that belong to resting populations whose numbers are controlled by homeostatic mechanisms (Fig. 1a). Upon activation,T cells undergo several rapid rounds of division, and then they stop dividing and most die. Some of the activated cells escape this activation-induced cell death (AICD) and (re-)enter the population of resting memory cells. An alternative explanation for the high turnover rates of T cells in HIV infection may be that a large number of cells stimulated by antigen and/or inflammatory molecules rapidly replicate and subsequently die, as opposed to the immune system responding to high rates of virus-mediated death with high rates of homeostatic proliferation.