Striking the right immune balance

Striking the right immune balance

Why do some people resist HIV while others quickly succumb to it? By studying populations in Kenya and Manitoba, researchers hope they will soon answer these questions and someday create an effective vaccine
November 30, 2012

For nearly a quarter-century, microbiologist Keith Fowke has been part of a University of Manitoba team of infectious disease specialists investigating an intriguing anomaly surrounding the human immunodeficiency virus (HIV) that leads to AIDS. Why are there sex trade workers in Nairobi, Kenya, who, despite being intensely exposed to HIV, do not become infected with the virus?

More recently, Fowke’s research has looked closer to home to ask the same question. In a study published this year, he and his colleagues looked at a number of Manitoba patients who had contracted HIV but did not require anti-viral drugs because of an immune response similar to that seen in the Nairobi sex trade workers. These patients are considered “elite controllers” of the disease.

Fowke is now beginning to investigate a third group of individuals who essentially represent the other end of the HIV spectrum. They are members of Winnipeg’s homeless and street population who are both solvent users and sufferers of an unusually rapid form of HIV — one that can result in the complete collapse of their immune system in a matter of months.

The potential links among these three groups is the focus of Fowke’s overall research, namely the relationship between HIV and CD4 positive T-cells — a type of white blood cell that regulates the body’s immune system.

HIV preferentially infects CD4 cells. And when viruses, bacteria or fungus invade the body, these cells are typically activated or “turned on.” Once activated, CD4 cells are more susceptible to HIV, which ultimately destroys them and sparks the chain of events that leads to HIV infection throughout the body.

“A consistent trait of the HIV-resistant Nairobi sex trade workers is that their immune system is not turned on or highly activated,” says Fowke. “Instead, it’s very calm and resting. So that’s a very difficult environment for HIV to make that initial foothold.”

Fowke, who calls this phenomenon “immune quiescence,” says something similar appears to be occurring in Manitoba’s “elite controllers.” Despite being infected by HIV, they do not require the usual drug treatment since their immune systems are controlling the level of virus in the blood.

These patients also had an immune system that was calm and unactivated. “They could fight HIV when they needed to,” he says. “So they were not providing more of those activated factories for HIV to infect and replicate in.”

On the other hand, the solvent users Fowke’s team is just beginning to investigate may be suffering from rapidly progressing HIV because of an over-activated immune system linked to substance abuse. Solvents, such as glue and lacquer, are extremely volatile and can damage tissue and cause inflammation — conditions that provide more of those activated target cells HIV thrives upon.

“Ultimately, what all of our research is hopefully leading towards is a vaccine or treatment that would mimic the immune system response that we are seeing in the HIV-resistant women in Kenya and in the elite controllers in Manitoba,” says Fowke.

But that’s no simple task. Fowke points out that the human immune system is a “complex, interconnected balancing act.” If it isn’t activated enough, humans can be susceptible to many other kinds of infection, but if it’s over-activated, it can open a path for HIV.

“This is a brand new avenue for consideration,” he says, “but it’s certainly worth trying to see if we can strike the right balance.”