Immune System Might Be Revived in Patients

A spirited race between top immunology teams is set to culminate today with the publication of two scientific papers reaching broadly similar conclusions about the AIDS virus: It exploits the human body's natural mechanism for shutting down the immune system, and the process can be reversed.

The findings raise the tantalizing possibility that doctors one day could switch a patient's immune system back on, so that it could resume its fight against HIV, or even cancer cells, certain parasites or the virus that causes hepatitis C. Those very different diseases "have one common denominator," says Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases. "They persist. They're chronic."
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Nevertheless, research in this area is exploding. The Bill and Melinda Gates Foundation is funding a team researching how to turn the immune system back on in hepatitis C patients. Researchers at the National Institutes of Health are studying PD-1 in tuberculosis, one of the world's leading killers.

"This isn't just HIV," says Harvard University immunologist Bruce Walker, the lead researcher on the study published in Nature. "This is much broader."

Research has progressed furthest in cancer, where scientists have shown that PD-1 can shut down immune responses when it is activated by certain types of tumor cells.
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The research being published today goes further to address one of the most vexing mysteries in the biology of AIDS. Key immune-system cells known as HIV-specific CD8 killer T-cells exist in high numbers in many HIV-infected patients. Early in the course of the infection, these cells kill other cells carrying the virus. But in long-term patients, these cells barely fight the virus at all. The reigning theory was that HIV somehow disabled them. That may still be true in part, but today's studies reveal that HIV actually exploits the body's own mechanism for shutting the cells down.

The PD-1 molecule buds on the surface of the killer T-cells that target HIV. By itself, PD-1 is inert and does nothing. But when PD-1 encounters a partner molecule, or ligand, the interaction sets off a chain reaction inside the killer T-cells. The T-cells multiply much more slowly or not at all, and overall they secrete far less of their powerful cytokines, the researchers found. Essentially, they abandon the fight.