Expansion, Maintenance, and Memory in NK and T Cells during Viral Infections: Responding to Pressures for Defense and Regulation

Immune responses are critical for defense. During primary infections, the antigen-specific CD8 T cells of the adaptive immune system are expanded from extremely low frequencies of cells and develop ‘‘memory’’ for heightened secondary responses. Innate natural killer (NK) cells, present at much higher frequencies, can also be expanded and develop memory. Subset NK and T cell proliferative responses are induced as a result of engagement of activator receptors for ligands expressed during particular viral infections, and the conditions are accompanied by stimulation of their antimicrobial functions. Increases in CD8 T cell numbers help optimize defense, but because of their higher basal frequencies, the need for increases in NK cell numbers is difficult to understand. The systems must have evolved under concurrent pressures for balance to limit damage from the immune responses themselves as well as to mediate defense against infection, however, as expanded NK and T cells present a threat for collateral damage. A recently defined function for an activating receptor in sustaining NK cells to produce interleukin (IL)-10 and regulate CD8 T cells is reviewed here in the context of T cell responses and memory. A rationale emerges for the role of proliferation in maintenance and regulation. The observations suggest that the immune system uses cell expansion to effectively deliver self-control as well as defense.