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

HIV infection leads to profound immune dysfunction. A number of immune cells are affected by HIV including both CD4 and CD8 T-cells. CD8 T-cells are essential to fighting viral infections and by limiting their activity HIV predisposes individuals to a number of opportunistic infections. Inactivating CD8 T-cells is also a likely means by which HIV itself evades the immune system. How HIV inactivates CD8 T-cells is not yet understood. IL-7 is a small protein carried in the blood that the immune system uses to activate CD8 T-cells. We have shown that the majority of CD8 T-cells in HIV+ patients do not express the receptor for IL-7 and thus cannot receive the activation signal. We have also shown that a protein produced by HIV known as Tat specifically down regulates the IL-7 receptor on healthy CD8 T-cells in culture. This research project seeks to determine exactly how the HIV Tat protein removes this essential IL-7 receptor from the surface of CD8 T-cells. Determining how this occurs is important to our understanding of how HIV causes immune dysfunction. This work is also expected to lead to new therapeutic strategies designed to increase immune function and potentially establish immunologic control of HIV infection.