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T cells activated to fight HIV basis for dendritic cell therapeutic vaccine

CD8 cells to more efficiently control HIV, the researchers focused on a molecule called interleuken-12 (IL-12). When dendritic cells recognize and capture viral antigens, they work together with CD4 T cells to release IL-12, which in turn triggers stimulation of killer CD8 cells that are specific to the virus.

Reporting at AIDS 2006, Xiao-Li Huang, M.D., research assistant professor of infectious diseases and microbiology at GSPH, said that IL-12 could be increased when CD40 ligand, a substance that binds to certain immune cells, and interferon gamma were added to dendritic cells.

In the study, white blood cells called monocytes were obtained from both HIV patients and individuals not infected with the virus. In the laboratory, the researchers coaxed them to differentiate into mature dendritic cells, and they were grown in culture with the addition of various substances to boost their potency. Separately, the researchers combined a small amount of the patient's HIV with their CD4 cells, in order to "super infect" them. In these now super-infected cells, the researchers inactivated the virus by promoting a process called apoptosis, or programmed cell death. In their dying state and with trace amounts of viral antigen still present, these CD4 cells were placed in culture with the beefed up dendritic cells. Recognizing the cells as foreign, the dendritic cells processed the antigen. Importantly, the dendritic cells presenting the HIV fragments were able to stimulate CD8 cells when the two cell types were combined.

"This model of T cell activation by dendritic cells provides a basis for immunotherapy trials of persons with HIV infection," said Dr. Huang.

The trial should be enrolling patients within the year, pending approval by the U.S. Food and Drug Administration. The researchers have already completed a similar trial in 18 patients that proved the approach is safe. In that trial, the vaccine was derived using a readily availab
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Source:University of Pittsburgh Medical Center


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