"Other researchers have seen low levels of killer T cells in so-called 'long-term non progressors,' HIV-infected individuals who have maintained unusually low levels of the virus for a very long time, which indicates to us that the body is adjusting to some sort of normal state," commented Dr. Rinaldo.
These findings raised the crucial question of whether the small numbers of memory killer T cells and their precursors, naive CD8 T cells, were capable of mounting a strong response against HIV-1. To answer this, the Pitt researchers used DCs, immune cells that can train killer T cells and other cells to destroy foreign substances while at the same time signaling them to attack.
DCs were taken from three HIV-infected study participants, stimulated with IL-12 and exposed to HIV-1 proteins encapsulated in a liposome, a tiny, fatty structure often used to deliver genes and other materials safely to the inside of a cell. The researchers found that DCs "pulsed" two to four times in laboratory dishes with the HIV-1 proteins and IL-12 were able to teach the killer T cells to recognize three important viral markers in HIV-infected cells. Recognizing these viral markers enables killer T cells to identify, attack and kill cells infected with HIV-1.
"We were encouraged to see that the killer T cells were ready, alert and
could attack HIV-infected cells after the dendritic cells gave them the signal.
By further stimulating naive T cells or boosting residual memory T cells with
therapeutic vaccines similar to the one we used in this study, it may be
possible to achieve complete immunity in patients. This would then allow a
patient's immune system to exert a much stronger control over HIV-1 i
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Contact: Amy Kemp
kempam@a1.isd.upmc.edu
412-624-2607
University of Pittsburgh Medical Center
29-Jun-1998