Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

Interleukin-7, a small protein carried in the blood, is currently being tested in clinical trials to help increase CD4 counts in HIV+ patients, and as a stimulant to vaccines in HIV+ individuals, cancer patients, and healthy volunteers. The effects of IL-7 on immune function, however, are not yet fuly understood. This research project seeks to determine how IL-7 affects CD8 T-cell function, cells that are essential to fighting viral infections. We hypothesize IL-7 activates two important signalling cascades within the cell each with different effects. One pathway removes the IL-7 receptor from the surface of the cell thus preventing further signalling and prepares the cell to fight infection. The other pathway stimulates the cell to proliferate. Interestingly, we have shown HIV is able to alter IL-7 signalling. By producing a small regulatory protein called Tat, HIV appears to enhance the IL-7 pathway that removes the receptor from the cell surface and inhibits the pathway leading to cell proliferation. By understanding how IL-7 works in CD8 T-cells and how HIV alters its function, we will be better equipped to use this immune modulator therapeutically and avoid adverse side-effects.