Immune cells given new life to fight HIV

TORONTO—A Canadian-U.S. research team has discovered a way to rejuvenate key virus-killing immune cells that become “exhausted” after a person is infected with HIV.
The scientists hope their work could lead to a whole new approach to therapy—bolstering the body’s natural ability to fight the disease by revitalizing these immune system cells, known as CD8 killer cells.

Co-author Dr. Mario Ostrowski, an infectious disease specialist at the University of Toronto, said that with most infections, such as influenza, CD8 killer cells are able to seek out and destroy other cells that have been infiltrated by a virus.
But with HIV, the CD8s “don’t produce all the chemicals required to kill infected cells,” he noted yesterday. “They can’t perform any function. . . . They’re just totally wimpy and exhausted.”
One thing the researchers discovered, however, is that these tired-out CD8 killer cells exhibit high levels of a molecule normally used to slow down the immune system after it has successfully dispatched a viral or bacterial invader.
In test-tube experiments on cells taken from people with HIV, the researchers found they could resurrect the CD8 killer cells by blocking this molecule, called Tim-3.
“We observed that blocking the Tim-3 pathway rescued those cells and restored their ability to fight off infection,” Ostrowski said.
The research, published in the Journal of Experimental Medicine, opens up the possibility of new therapies aimed at blocking the Tim-3 signal and reinvigorating the immune system’s natural disease-fighting ability.
Currently, the most effective HIV treatments are antiviral drugs that stop the virus from replicating. But they only work in about 80 percent of infected people and have to be taken for life.
If the drugs are stopped, the virus soon begins its relentless destruction of the body’s immune system.
“We still do not know how the virus triggers Tim-3 or if this is restricted to HIV infection,” said co-principal author Dr. Lishomwa Ndhlovu of the University of California at San Francisco.
“But our findings may provide a new direction to vaccines and therapies that will potentially reverse these dysfunctional cells and allow them to control HIV-1 replication,” Ndhlovu said in a release.
Commenting on the research, some HIV-AIDS experts hailed the work as innovative and promising, but cautioned that it is early days yet.
“I think it’s a wonderful study,” said Dr. Mark Wainberg, director of the McGill AIDS Centre at Jewish General Hospital in Montreal.
“Of course, this is not something that’s going to be easily translated into patient benefit in the short term,” he added. “But it provides insight into how the immune system breaks down after HIV infection occurs, as well as into what we might need to do in order to try to bolster immunity in people who have HIV disease.”