Purpose of review: To describe the recent data on the role of coinhibitory receptors, such as PD-1, Tim-3, CD160, as mediators of the ‘exhaustion’ of virus-specific CD8 T cells in chronic infections and particularly in HIV.
Recent findings: Exhaustion of chronic virus-specific CD8 T cells is a dynamic process characterized by altered differentiation, impaired function, and compromised proliferation/survival profile of these cells. This process is mediated by coinhibitory receptors expressed on the surface of virus-specific CD8 T cells and an orchestrated function of centrally connected pathways. Coexpression of several coinhibitory receptors characterizes severely exhausted virus-specific CD8 T cells. Several studies suggest a synergistic action, instead of a redundant role, of the different receptors. In-vivo manipulation of the coinhibitory network can rejuvenate exhausted virus-specific CD8 T cell responses and constrain replication of chronic viruses, including HIV.
Summary: Revealing the molecular basis of virus-specific CD8 T cell exhaustion in chronic infections is critical for the understanding of the disease pathogenesis and the designing of novel vaccines aiming to enhance the cytolytic arm of the immune system. This is of particular interest for the development of immunotherapies in the context of a functional cure for HIV.