The Sequence of S1P Receptor-regulated Events
n Thymic Maturation and Egress.

Shown are the sequence of S1P receptor-regulated events in thymic maturation and egress based on phenotypic and positional changes within medullary populations, the effects of pertussis toxin, and formal evidence for the inhibition of thymic emigration. Double positive CD69(+) T cells are found in the cortex, whereas single positive CD69(+) T cells are found in the medulla except in the presence of pertussis toxin when single positive CD69(+) T cells remain in the cortex. An S1P receptor activation-independent step results in generation of a population of CD69(int) single positive T cells, which then undergo rapid maturation to CD69(-) single positive cells induced by S1P receptor agonism. The egress of all mature cells is then rapidly negatively regulated by S1P receptor activation, inhibiting the CCR7(-) dependent appearance of mature cells in secondary lymphoid organs. Figure Copyright ©2003, The Proceedings of the National Academy of Sciences.