Grant: Operating Grant

One of the greatest mysteries of Human Immunodeficiency Virus Type 1 (HIV) 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 dys-functional, or 'exhausted'. Recently a clue to why these T cells are exhausted was demonstrated by numerous publications that have identified some new molecules on these cells that may explain their exhaustion. Our lab has identified one of these new molecules 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, and is actually in part responsible for their exhausted state. Our current work centers on understanding how this Tim-3 molecule can make a killer T cell weak and also to figure out what signals the Tim-3 molecule sends to the T cell in order it to shut down. Our main aim it to find new ways of stopping the Tim-3 from sending 'weakening' messages to the T cell and by blocking Tim-3 signals so that the T cells can function better with the aim to allow these cells to eradicate HIV in the infected person.