The integration of T cell migration, differentiation and function

Key Points Although the classical model of T cell entry into secondary lymphoid organs suggests that this requires CD62L, CC-chemokine receptor 7 (CCR7) and lymphocyte function-associated antigen 1 (LFA1) to support the rolling, activation and arrest of T cells at high endothelial venules, the rules are different for T cell entry in mucosal-associated lymphoid tissue, splenic white pulp and inflamed lymph nodes. T cells may also enter a lymph node downstream of a neighbouring lymph node via the afferent lymphatics. Intranodal motility is regulated by CCR7, while egress of T cells is dictated by responsiveness to sphingosine-1-phosphate (S1P) gradients. Migration of activated T cells into non-lymphoid tissues may be somewhat promiscuous; however, it is influenced by developmental cues that reflect the site of T cell priming as well as the inflammatory status of the target tissue. Effector T cells use various strategies to increase the efficiency of their scanning for antigen in non-lymphoid tissues. These strategies include the use of Lévy walks and adopting a 'dendritic-like' morphology in order to simultaneously contact multiple targets. After pathogen clearance, memory T cells found in non-lymphoid tissues are either tissue-resident or re-circulating. Resident memory T cells adapt their phenotype in response to local cues within non-lymphoid tissues, and this may optimize site-specific protective immune responses by affecting T cell function and allowing for their long-term maintenance within these unique environments. Non-lymphoid organs comprise many tissue types and compartments, each of which may be populated by different T cell subsets. Histological analyses as well as intravascular labelling of capillary-bound T cells may be necessary to place populations in their proper anatomical context. The central memory T cell and effector memory T cell nomenclature suffers from an absence of universally accepted definitions. Refining these terms will be necessary for the field to optimally conceptualize and communicate the additional complexity of migration and location-dependent T cell differentiation states that have recently been characterized. Here, the authors describe how T cell trafficking to distinct tissues is regulated under inflammatory and non-inflammatory conditions. They explain how the unique migratory properties of different T cell populations are intimately connected to their functions and, furthermore, discuss whether the ever-expanding nom