FTY720: a new dimension in transplantation.

IN CONTRAST TO the subfamily of neutrophil and mononuclear chemotactic cytokines (chemokines) upregulated by inflammation, FTY720 seems to affect the interactions of lymphocytes with the subfamily of homing chemokines, secondary lymphoid tissue chemokine (SLC) and essential myosin light chain chemokine (ELC). These homing chemokines are constitutively expressed in T-cell zones of secondary lymphoid structures (SLS), including peripheral lymph nodes (PLN), Peyer’s patches (PP), appendix, and spleen (SPL), wherein they attract lymphocytes and dendritic cells bearing the corresponding receptors CCR7 or CXCR3 (SLC) or only CCR7 (ELC). The chemokine receptor CCR7 is expressed on stomal elements within T-cell zones, on dendritic cells (DC), on B cells, on T lymphocytes bearing the Th1 as opposed to Th2 phenotype, and on memory cells remaining within SLS in contrast to the circulating effectors that generate inflammatory mediators. (CCR7 is not present on granulocytes or monocytes.) Following binding of CCR7 to ELC and SLC, lymphocytes display activation of integrin adhesion molecules, events necessary for incorporation into the critical microenvironment for immune maturation. Indeed, cells from CCR7 knockout (KO) mice fail to develop delayedtype hypersensitivity reactions or primary antibody responses.