Immune System Cells Might Be Revived to Fight HIV, Studies Say

The process that renders immune system cells ineffective in fighting HIV potentially can be reversed, according to studies published in the journals Nature and Nature Medicine, the Wall Street Journal reports. Both studies looked at the molecule programmed death-1, which is found on the surface of T cells and regulates T cell function, according to the Journal (Schoofs, Wall Street Journal, 8/21). In one study published in Nature, Bruce Walker, director of Partners AIDS Research Center at Massachusetts General Hospital, and colleagues analyzed blood samples from 71 newly diagnosed HIV-positive people who had not begun antiretroviral treatment. The researchers also analyzed blood samples from HIV-positive people after they had begun antiretroviral treatment. The study finds that HIV infection triggers activation of the PD-1 molecules, which impedes T-cell multiplication. In addition, the higher the amount of activated PD-1, the greater the impairment of the T cells, according to the study. The study also finds that HIV treatment decreased the amount of activated PD-1 molecules and increased T cell function. Walker said, "Currently, we just count the number of T cells to decide when to treat someone, but we are excited about the possibility that adding PD-1 measurements might tell us more about the likelihood of progression of the disease and need for treatment in infected people" (BBC News, 8/20). In a separate study published in Nature Medicine, Rafick Sekaly, a professor at Canada's Universite de Montreal, and colleagues found the same process is true for CD8+ T cells. The study finds that when PD-1 combines with its ligand, the T cells multiply more slowly or stop reproducing. The researchers also found that when an antibody that blocks the interaction between PD-1 and its ligand was added to a test tube, the T cells began to multiply again.

Implications, Next Steps
Although there needs to be further research in this area, the studies "suggest that two critical types of immune system cells -- CD8 and CD4 -- can in most patients be rescued and remobilized to fight HIV," according to the Journal. However, the findings are preliminary, and there is no guarantee that they will provide data that lead to new treatments, the Journal reports. In addition, deactivating PD-1 molecules might trigger an autoimmune disease, according to the Journal (Wall Street Journal, 8/21). Walker said, "One has to proceed with real caution because if you turn back on an immune regulatory switch that the body has decided to turn off, you could trigger serious immunological problems." Walker said the next step in research will be to determine if PD-1 can be deactivated in HIV-positive people without causing them serious side effects (BBC News, 8/20). Another study, led by Richard Koup, chief of the immunology laboratory at NIH's Vaccine Research Center, finds that interaction between PD-1 and its ligand causes CD8+ T cells to die. The study is expected to be published in the Sept. 5 online edition of the Journal of Experimental Medicine (Wall Street Journal, 8/21).

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