Role of Regulatory T Cells and Inhibitory Molecules in the Development of Immune Exhaustion During Human Immunodeficiency Virus Type 1 Infection

One of the key hallmarks of chronic human immunodeficiency virus type 1 (HIV-1) infection is the persistent immune activation triggered since early stages of the infection, followed by the development of an exhaustion phenomena, which leads to the inability of immune cells to respond appropriately to the virus and other pathogens, constituting the acquired immunodeficiency syndrome (AIDS); this exhausting state is characterized by a loss of effector functions of immune cells such as proliferation, production of cytokine, as well as cytotoxic potential and it has been attributable to an increased response of regulatory T cells and recently also to the expression in different cell populations of inhibitory molecules, such as programmed death receptor-1 (PD-1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell immunoglobulin-3 (Tim-3), and lymphocyte activation gene-3 (LAG-3). The importance of these molecules relies on the possibility to restore the immune response once these molecules are blocked, constituting a potential therapeutic target for treatment during HIV infection. In this regard, we explored the available data evaluating the functional role of Treg cells and inhibitory molecules during the infection in both blood and gut-associated lymphoid tissue (GALT) and their contribution to the development of immune exhaustion and progression to AIDS, as well as their therapeutic potential.