Immune system boosting hormone might lead to HIV cure

Chronic viral infections can sometimes overwhelm the immune system, leading to a phenomenon some call "immune exhaustion." When this happens, the immune system is no longer able to fight back effectively against the infection.

Now researchers led by Dr Marc Pellegrini from the Walter and Eliza Hall Institute in Melbourne have shown that boosting the immune system in mice can rid them of a chronic infection by an HIV-like virus.

The finding opens up the possibility of using this immune boosting technique to combat chronic infections like HIV, hepatitis and tuberculosis.

The researchers set out to investigate the mechanisms responsible for immune exhaustion, and to see if they might be reversed.

It was believed that some system was acting to suppress the immune system in cases of chronic infection in order to prevent the immune system overreacting and possibly damaging other tissue.

They hypothesised that a cell signalling hormone called interleukin-7 (IL-7), which is known for overcoming inhibitory mechanisms, might be able to prevent this suppression of the immune system.

The infected mice with a virus, Lymphocytic chorimeningitis virus (LCMV) variant clone 13, which establishes a chronic infection similar to that produced by HIV.

They then injected the mice with human IL-7 and found the mice experienced a "profound" boost to immune response and were able to eliminate the infection entirely.

The mice experienced increased thymic output and saw an increase in T cell numbers, both T cells that targeted LCMV and other types of T cells as well.

According to Pellegrini, the mechanism at work behind the scenes was that IL-7 was able to downregulate another protein, SOCS-3, in T cells.

It was SOCS-3 that was putting the breaks on the immune system in cases of chronic infection and preventing the body from potentially attacking itself.

“In an overwhelming infection, SOCS-3 becomes highly activated and suppresses the immune response, probably as a natural precaution to prevent ‘out-of-control’ responses that cause collateral damage to body tissue,” said Pellegrini.

“In the case of these overwhelming infections, the immune system effectively slams on the brakes too early, and the infection persists.”

By downregulating Soc3, the immune system was able to bounce back and clear the infection, although not without some collateral damage to other tissue caused by the highly active immune system.

“The key for us was figuring out that turning off SOCS-3 only really worked when it was within T cells,” said Simon Preston, a co-author on the paper.

“It allowed the immune response to boost the number of virus-specific T cells and have an immune response good enough to eliminate the virus without initiating an immune response that was too large and would make the animal sick.”

This finding could have tremendous significance in the field of combating chronic infection, and could lead to new therapies that might even lead to a cure for HIV.

“The findings could help to develop drugs that target some of these host molecules, such as SOCS-3, and turn them off for very short, defined periods of time to reinvigorate the T cells, allowing them to regroup to fight infection,” said Pellegrini.

The researchers suggest that IL-7 treatment might produce a potent antiviral response while the patient is undergoing antiretroviral treatment to reduce the viral load. In this situation, it's possible the body might be able to eradicate the infection.

The study was published in the journal, Cell, and was supported by the National Health and Medical Research Council, the Canadian Institute for Health and the Cancer Research Institute.