4 December 2008

Why some people are immune to AIDS

Cosmos Online
Experts say they have discovered why some people have a natural immunity to HIV – a breakthrough which could lead to new treatments.
killer T-cell

Path to new treatment?: A microscope image of a CD8+ T cell loaded with perforin and granzymes. Highlighted with flourescent markers, perforin is in green, granzyme B in white and a stain for HIV-specific killer T-cells is in red. Credit: Mark Connors

LONDON: Experts say they have discovered why some people have a natural immunity to HIV – a breakthrough which could lead to new treatments.

A new study, published today in the journal Immunity, identifies the mechanism by which these people, called long-term non-progressors, are able to control the virus, preventing the development of full-blown AIDS.

This represents “a tremendous boon to the field” of HIV vaccine research, said Mark Connors, co-author and an immunologist at the U.S. National Institutes of Health in Bethesda, Maryland.

Natural born killers

“Some people [less than 0.5 per cent] control the infection even decades after they were first infected” he said. Previous research suggested that this control had something to do with a certain type of immune cell – CD8+ T cells, which find and destroy other cells infected with the virus – but precisely why has remained a mystery.

Now Connors and his team have discovered that the CD8+ T cells of naturally immune people control the disease by delivering deadly poisons to the infected cells.

To make the discovery, the scientists developed a series of sensitive assays that tested the presence of these T cells, and their ability to kill HIV-infected cells. They found that the proliferation ability of the CD8+ T cells was greater in infected people who could control the disease than in those who could not.

But they also found that it was not just the number of these cells that mattered, but their mode of action too – the cells that confer useful immunity were able to create and deliver a pair of deadly molecules dubbed ‘perforin’ and ‘granzyme B’.

Perforin, as its name implies, pokes holes in the membranes of target cells. This action then allows granzyme B to enter and kill the infected cell.

Challenging a long-held paradigm

The results challenge a long-held paradigm that our immune memory cells, such as CD8+ T cells, are just “sitting there with a loaded gun, with all the bullets they need to kill the virus,” said Connors. It seems that, in reality, these “memory cells need to be re-stimulated” on repeated encounters with the virus in order to protect us, he said.

“In terms of developing a vaccine, this gives us a new and important parameter to look at when we are evaluating candidates for efficacy” commented Joel Blankson a medical scientist from John Hopkins University, in Baltimore, Maryland, who was not involved with the work.

He added that the study is “also an important proof-of-concept because it shows that with the right stimulus, HIV-specific killer T cells… can be coaxed into efficiently killing HIV infected cells.”

Therapeutic vaccine

This means that we might one day be able to create a ‘therapeutic’ vaccine which can actually fight the infection, rather than only conferring protection in advance of contracting HIV.

Guido Silvestri, an immunologist at the University of Pennsylvania, in Philadelphia, said that he has big hopes for the research.

“It is likely that studies like this one will eventually pave the way for immune-based interventions that may harness the human immune system in ways that will result in complete control, or even eradication, of HIV,” he said. “Of course we have a long way to go, 10 to 20 years at least, but this is a step in the right direction.”

Connors said the next question for his team is why CD8+ T cells in most people lack this ability to kill HIV-infected cells.


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