T cell trafficking and metabolism: novel mechanisms and targets for immunomodulation

Coordinated migratory events by naïve and memory T cells are key to effective immunity. Naïve T cells predominantly recirculate through secondary lymphoid tissue until antigen encounter, while primed T cells efficiently localize to antigen-rich lymphoid and non-lymphoid tissue. Tissue-selective targeting by primed T cells is achieved by a combination of inflammatory signals and tissue-selective homing receptors acquired by T cells during activation and differentiation. A large number of molecular mediators and interactions promoting memory T cell migration to non-lymphoid sites of inflammation have been identified. Recently, additional antigen-driven mechanisms have been proposed, which orchestrate the targeted delivery of memory T cells to antigen-rich tissue. Importantly, recent studies have revealed that the T cell metabolic status influences their differentiation and homing patterns. We here summarize these key observations and discuss their relevance for the manipulation of immune anatomy in therapeutic settings.

► Specific area codes address T cells to target tissues. ► Antigen recognition and costimulatory molecules regulate T cell migration. ► The PI3K–AKT–mTOR metabolic pathway controls T cell migration.