Tertiary lymphoid structures, a historical reappraisal

Tertiary lymphoid structures (TLSs) are accumulations of lymphoid cells within non-lymphoid organs that share the cellular compartments, spatial organization, vasculature, chemokines, and function with secondary lymphoid organs, especially lymph nodes. TLSs are organized into a separate T cell compartment and B cell compartment which contain germinal centers with follicular dendritic cells. In most cases, TLSs contain Peripheral Node addressin (PNAD) expressing high endothelial venules (HEVs). TLSs have been described in various mouse models of inflammation and are associated with a wide range of autoimmune diseases. Other than these, TLSs have been described in chronic allograft rejection and cancer.