How HIV outsmarts the immune system

This article is more than 22 years old.

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.

Glossary

T killer cell

A type of immune cell that can kill certain cells, including foreign cells, cancer cells, and cells infected with a virus. A T killer cell is a type of white blood cell and a type of lymphocyte. Also called cytotoxic T cell, cytotoxic T lymphocyte or CD8 T cells. 

killer T cells

A type of immune cell that can kill certain cells, including foreign cells, cancer cells, and cells infected with a virus. A T killer cell is a type of white blood cell and a type of lymphocyte. Also called cytotoxic T cell, cytotoxic T lymphocyte or CD8 T cells. 

strain

A variant characterised by a specific genotype.

 

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

target cell

Type of cell that HIV or another virus or bacteria infects.

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.

References

Lee SK et al. The functional CD8 T cell response to HIV becomes type-specific in progressive disease. J Clin Invest. 110 (9): 1339-1347, 2002.