TNF family ligands define niches for T cell memory

Immunological memory is a critical feature of the adaptive immune system and the underlying principal behind vaccination. The mechanisms that maintain memory T cell survival between the initial and subsequent encounter with antigen remain incompletely defined. Although the cytokines IL-15 and IL-7 are important in memory T cell homeostasis, additional signals by way of TNFR family members are required for maximal maintenance of T cell memory. Here we propose a unifying model in which subsets of TNF family ligands distinguish the competitive niches for maintenance of CD4 versus CD8 T cell memory. Understanding the unique ‘memory niches’ defined by TNF family ligand expression will provide new insights into the mechanisms of memory T cell maintenance.