Project 170729

One of the greatest mysteries of Human Immunodeficiency Virus Type 1 (HIV-1) infection has been to understand why the normal immune system is unable to eradicate or control this virus infection as opposed to other virus infections. Our laboratory specializes in understanding how one arm of the immune system, called the T cells, fights viruses, including HIV-1 virus, the virus that causes AIDS (acquired immunodeficiency syndrome). It has been found that these T cells that are supposed to fight HIV-1 do a bad job, and have been called dysfunctional, or exhausted. Recently a clue to why these T cells are exhausted was demonstrated by numerous publications that have identified a new molecule on the surface of these exhausted cells called PD-1. We have now identified, another new molecule on the surface of these exhausted T cells called Tim-3 (T cell immunoglobulin mucin molecule type 3). We have found that Tim-3 identifies the most exhausted of these T cells. We also show that by blocking the action of this Tim-3 molecule on the T cell, we can rescue the function of these cells to fight HIV better. The current project will try to understand why Tim-3 is increased in HIV infection in order to develop new therapies to block the actions of Tim-3 so that infected persons can fight the virus better and possibly get rid of it, as well as develop new ways of vaccinating against the virus in uninfected persons.

investigating Tim-3 as a novel therapeutic target to reverse T cell exhaustion in HIV-1 infection