UC DAVIS (US) — Tissue infected with a close relative of HIV can ramp up production of a type of T cell that actually weakens the body’s attack against the invading virus.
The discovery, in lymph nodes draining the intestinal tract, could help explain how the HIV virus evades the body’s immune defenses. The findings, based on a study with monkeys, are reported in the journal AIDS.
If the same pattern is found in people infected with HIV, it could lead to a treatment strategy that slows the production of the restraining type of T cell clearing the way for immune soldiers to go after the virus more aggressively.
Scientists don’t yet know if the simian virus is directly causing the build-up of the inhibitory T cells, called regulatory T cells, but in any case, they say reducing regulatory T-cell production could boost the body’s resistance to the evasive virus.
Regulatory T cells, or Tregs, normally tamp down immune-system attacks, presumably to prevent an over-active assault that can cause harmful inflammation or auto-immune disease. The scientists suspect that the high number of Treg cells in the infected primates might prevent their immune systems from mounting a full-on attack against the virus.
The researchers focused on immune cells called dendritic cells that interact with Tregs in preparation for their policing duty. This occurs in lymph nodes throughout the body’s lymphatic system—the part of the circulatory system that also drains many organs of fluids, fatty acids and other substances.
Mature dendritic cells are particularly active in promoting Treg production, and are in high concentration in nodes draining the intestine, or mucosa. The intestinal mucosa is the site of early infection and aggressive transmission for both the primate virus and HIV, making it the first line of defense against the invasion.
“The intestinal mucosa contains highly activated ‘helper’ T-cells that are prime targets for the HIV virus, so it is important to understand how the body fights HIV in this under-studied tissue,” says Barbara Shacklett, associate professor of medical microbiology and immunology at the University of California, Davis.
“We consider the GI tract as a major battlefield between the immune system and HIV. If we can better understand what happens there, we may finally learn how to eradicate the virus.”
An editorial in the same issue of AIDS highlights the new research and related studies that are clarifying the interaction between the simian version of HIV and the Treg cells that can control attacks against them.
Tregs usually increase when the immune system is at risk of over-reacting, Shacklett says. Their high numbers lead to a reduced immune attack, although the mechanism is not well understood.
But in persistent infections—when a strong immune response is called for—Tregs should decrease in number, taking a “hands-off” approach and freeing the immune army to advance. HIV may sabotage this control by prompting increased Treg production as if the body need not rally its defenses against the virus.
The research draws on earlier research by Shacklett and colleagues comparing Treg counts in rectal mucosa of people with high and low HIV viral load. They showed that high viral load was associated with increased frequencies of immunosuppressive Treg in the gastrointestinal mucosa, suggesting these Tregs might be thwarting the body’s immune defenses.
Other coauthors on the new research paper are from the University of Cincinnati College of Medicine, and the California National Primate Research Center.
The research was supported in part by the California National Primate Research and the National Institutes of Health.
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