Regulation of global CD8⁺ T-cell positioning by the actomyosin cytoskeleton

CD8⁺ T cells have evolved as one of the most motile mammalian cell types, designed to continuously scan peptide-major histocompatibility complexes class I on the surfaces of other cells. Chemoattractants and adhesion molecules direct CD8⁺ T-cell homing to and migration within secondary lymphoid organs, where these cells colocalize with antigen-presenting dendritic cells in confined tissue volumes. CD8⁺ T-cell activation induces a switch to infiltration of non-lymphoid tissue (NLT), which differ in their topology and biophysical properties from lymphoid tissue. Here, we provide a short overview on regulation of organism-wide trafficking patterns during naive T-cell recirculation and their switch to non-lymphoid tissue homing during activation. The migratory lifestyle of CD8⁺ T cells is regulated by their actomyosin cytoskeleton, which translates chemical signals from surface receptors into mechanical work. We explore how properties of the actomyosin cytoskeleton and its regulators affect CD8⁺ T cell function in lymphoid and non-lymphoid tissue, combining recent findings in the field of cell migration and actin network regulation with tissue anatomy. Finally, we hypothesize that under certain conditions, intrinsic regulation of actomyosin dynamics may render NLT CD8⁺ T-cell populations less dependent on input from extrinsic signals during tissue scanning.