'Switch' may turn off immune cells that fight HIV

Aug 20 2006

An international research team believe they have discovered why the immune system is unable to control HIV infection.

The team have found a molecular pathway involved in the immune cell "exhaustion", present in other chronic viral infections, also plays a similar role in HIV infection.

They have also found that blocking the pathway restores some function to HIV-specific CD8 and CD4 T cells.

The researchers from the Partners AIDS Research Center at Massachusetts General Hospital (MGH), the University of KwaZulu-Natal (UKZN) in South Africa, and other institutions, say HIV evades the body's natural defences against viral infections by disarming the T cells sent by the body to fight it, by flicking a molecular switch on the cells.

They say they were able to block this switch and restore T cell function in the laboratory.

The researchers say that though drugs are already available that can do the same thing, more safety studies are needed as the drugs may not be specific enough and could cause serious adverse effects.

Dr. Bruce Walker, director of the Partners AIDS Research Center and principal investigator of the study says in 1987 the MGH team confirmed the existence of HIV-specific CD8 cells, the cytotoxic T lymphoctyes that should destroy virus-infected cells.

These cells were found in high numbers in people with the late stages of AIDs, which was odd as that indicated that they were somehow not doing their job.

This led to the discovery that though the cells were there they had some how been turned off in persons with high viral infections.

The T cell switch apparently controls a pathway of cellular events called programmed death-1 or PD-1.

The researchers, studied blood samples from 71 people who had recently contracted HIV but who had not yet commenced anti-HIV treatment and also examined samples from four HIV-positive individuals taken before and after they had begun antiretroviral therapy.

It appeared that HIV turned the T cell switch off, triggering the inhibitory PD-1 pathway and this in turn was associated with more severe functional impairment of T cells.

When HIV treatment began, however, blocking the PD-1 pathway, the T cell function was restored.

The researchers say the next step will be to see if the T cells can be turned back on in HIV-infected people in a way that will benefit them without incurring any serious side effects.

They are also exploring whether PD-1 measurements could be used to guide treatment.

Dr Walker, a professor of Medicine at Harvard Medical School and a Howard Hughes Medical Institute investigator, says at present to decide when to treat someone, the number of T cells is counted, but the possibility that adding PD-1 measurement might give more information about the likely progression of the disease and need for treatment in infected people, is he says exciting.

Experts and specialist in HIV and AIDS say the study is promising and encouraging, and fills another gap in scientists' knowledge about how HIV functions.

They hope that it will lead to new therapies to treat and prevent the disease within the coming decade.

The study is published in the journal Nature.