Figure 1.

T cell differentiation during acute vs. chronic infections. When pathogenic peptides are presented by major histocompatibility complex (MHC) to naive T cells during infection, corresponding T cells are activated and differentiate into effector T cells specific for the pathogen. During acute infection, the immune system is able to specifically target the pathogen and eradicate it. During this process, memory T cells develop and confer immunological memory against recurrent infection. In contrast, during chronic infection the persistent load of pathogenic peptides leads to permanent stimulation of T cells, which promotes T cell exhaustion. T cell exhaustion is in part defined by the upregulation of coinhibitory receptors such as PD-1, LAG-3, and Tim-3. These receptors inhibit T cells by decreasing IL-2 production, proliferation, and the threshold for apoptosis.