How HIV outsmarts the immune system

New data has emerged to explain how HIV outsmarts the immune system in the later stages of HIV infection. Although we know that HIV infects the immune system's helper T cells (CD4+ cells), killer T cells (CD8+ cells) are not infected. Consequently, while helper T cells decline as HIV disease progresses, there are often large numbers of killer T cells until HIV progresses to AIDS. Until now, it was not understood why these killer T cells stopped being effective.

In an article in the November 4 issue of the Journal of Clinical Investigation, Premlata Shankar and colleagues from the Centre for Blood Research at Harvard Medical School reveal that late in HIV disease, CD8+ cells are still able to kill laboratory strains of HIV. However, they are progressively less able to recognise and kill HIV that comes from our own bodies. The researchers believe this is due to the virus' tendency to mutate and the inability of the weakened immune system to keep up with the changing virus.

The researchers compared killer T cells from HIV infected asymptomatic individuals with those from symptomatic AIDS patients. They examined the killer cells' ability to eliminate target cells infected with laboratory strains of HIV on one hand, and with virus isolated from the patient on the other. What they found is that killer T cells from asymptomatic individuals can recognize and kill both types of target cells. In contrast, the killer T cells from symptomatic patients, while still able to recognize and eliminate the laboratory strain targets, no longer killed target cells that were infected with their own virus.

While there may still be high numbers of killer T cells late in HIV disease, the researchers found that they are likely to be programmed only to kill wild-type HIV (i.e. non-mutated virus). As HIV mutates in the body due to several factors - including pressure from antiretroviral medications - these killer T cells become increasingly irrelevant. Without helper T cells - which slowly disappear during HIV disease - the killer T cells are unable to programme themselves to recognise the increasingly diverse population of HIV inside the body.

These findings are significant because they show that conventional measurements of killer T cell responses in people with HIV - which focus on responses to laboratory strains - overestimate the response to the person's own virus, and the authors emphasize the need to develop more accurate, and therefore relevant, measurements.