Grant: Operating Grant - PA: HIV/AIDS Bridge Funding - Biomedical/Clinical Stream

HIV is known to cause defects of the immune system which are the hallmark of HIV disease. Despite the increasing availability of antiretroviral drugs (ART) to treat HIV infections, we are still unable to completely restore the function of the immune system in people who are infected with the virus. One part of the immune system that does not recover in individuals taking ART is called the innate immune system, and the reasons why the innate immune system remains non-functional are not well understood. Over the course of many years of an HIV infection, constant exposure to the virus causes cells of the immune system begin to display markers on their surface that inhibit their function. This project focuses on the expression of one of these markers, called LAG-3, and its expression on cells of the earliest phase of immunity called the innate immune system. Our published data indicates that LAG-3 is at least partially responsible for some of the defects that occur in innate immunity, regardless of whether someone is taking ART or not. The goal of this proposal is to determine exactly what role LAG-3 might play in inhibiting the immune system, and whether its effects can be blocked in order to boost the immune response. It will also determine what causes LAG-3 to be expressed on immune cells, and which immune cells produce more or less LAG-3. This research will allow us to test whether blocking LAG-3 could be part of new treatment options for HIV infection.