Some people with HIV are able to keep the virus under control without any need for drugs, and researchers are now a step closer to understanding how their bodies do it. The finding could open up new approaches for possible vaccines and treatments.
When HIV gets into the body, it infects and kills a certain type of immune cell called T cells. These circulate through the blood where they fight infection, but they actually spend most of their time in patches of immune and connective tissue 鈥� called lymphoid tissue 鈥� in places like the gut and lymph nodes. However, almost all HIV research into T cells has been based on those found in blood, because they鈥檙e much easier to study. This has led to a skewed picture of how our immune systems respond to the virus.
Marcus Buggert, while at the University of Pennsylvania, began investigating the T cells in lymphoid tissue. He and his colleagues were particularly interested in how T cells might behave differently in the lymphoid tissue of people who are HIV 鈥渆lite controllers鈥�. These people make up only a fraction of one per cent of those infected with HIV, and can naturally control the virus for decades without any drugs.
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Special cells
Previous work has found that genetics seems to play a role in being an elite controller. These people also have immune cells that are more effective at killing HIV-infected cells in the blood. These cells are called CD8 T cells, and seem to work better in the blood of people elite controllers than in other people.
But blood is only part of the story when it comes to HIV infection, and one of the reasons it鈥檚 so difficult to eliminate the virus is because most of it hides out in the body鈥檚 tissues. Now it seems that elite controllers have an advantage there too.
Buggert鈥檚 team found that, in elite controllers, large numbers of CD8 T cells move into the lymphoid tissue and stay there. When they get there, they express different genes, make different proteins, and carry tags on their surface that stop them from being removed and returned to the blood. People who have HIV but are not elite controllers have only a few of these modified cells.
Hidden virus
In unpublished work, the team have found that these modified cells appear to keep HIV in check in the lymphoid tissue, but we don鈥檛 yet know how. While CD8 T cells in the blood simply kill HIV-infected cells they encounter there, that doesn鈥檛 seem to be the case in the lymphoid tissue.
Because HIV-infected cells are thought to spend only 10 per cent of their time in the blood, this insight could have big implications for new approaches to seek out and destroy infected cells that are hiding in the body鈥檚 tissues.
This work is the first step towards understanding how some people keep the HIV virus under control, says Nadia Roan, at the University of California, San Francisco. She says the findings should inform efforts to design vaccines and functional cures for the virus.
Journal reference: Science Immunology
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