Figure 2.

Differential T-cell responses to short-term (acute) and long-term (chronic) infections. (A) In acute infections (solid black line), T-cell response spikes are marked by acquisition of effector function (e.g., cytokine production) and upregulation of activation markers and clonal expansion. When an infection or antigen is cleared, a small subset of effector T cells differentiate into memory cells, poised to reactivate upon re-infection, while most cells die. However, if the antigen level or inflammation persists as in the case during chronic infections, T cells develop into a distinct subset, termed “exhausted” T cells (solid red line). (B) Among the characteristics that define exhausted T cells are 1) coordinate expression of multiple immunoregulatory receptors, 2) decreased effector function, 3) altered metabolic function, and 4) altered transcriptional and epigenetic status.