NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections

Viral infections characteristically induce a cytokine-driven activated natural killer (NK) cell response that precedes an antigen-driven T cell response. These NK cells can restrain some but not all viral infections by attacking virus-infected cells and can thereby provide time for an effective T cell response to mobilize. Recent studies have revealed an additional immunoregulatory role for the NK cells, where they inhibit the size and functionality of the T cell response, regardless of whether the viruses are themselves sensitive to NK cells. This subsequent change in T cell dynamics can alter patterns of immunopathology and persistence and implicates NK cells as rheostat-like regulators of persistent infections.

► Activated NK cells lyse activated CD4 T cells and in so doing inhibit both CD4 and CD8 T cell responses. ► NK cell mediated suppression of T cell responses changes patterns of viral pathogenesis and persistence. ► NK cells indirectly regulate the clonal exhaustion of T cells and may be needed to maintain persistent infections.