Environmental cues orchestrate regional immune surveillance and protection by pulmonary CTLs

Tissue-resident memory CD8 T cells (T_RM) provide preemptive immunity against infections that begin in peripheral tissues by guarding the site of initial pathogen exposure. Their role in immunity to respiratory virus infection is particularly important because severe damage to the alveoli can be avoided when local populations of T_RM cells reduce viral burdens and dampen the responses of effector CD8 T cells in the lungs. Although a connection between rapid immune activation and early viral control is well established, the signals that keep T_RM cells poised for action in the local tissues remain poorly defined. Recent studies have shown that environmental cues influence the fate decisions of activated CTLs during memory formation. Manipulation of these signaling pathways could provide new ways to capitalize on protection from T_RM cells in mucosal tissues, while reducing collateral damage and pathology during vaccination.