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Chapter 13 Chemokines and Hematopoietic Cell Trafficking 143

lymphoid organs through efferent lymph vessels or, in the case of the SUMMARY
spleen, by directly returning to the blood. Several adhesion receptors
have been implicated in the egress of lymphocytes into lymphoid In this chapter we have outlined three distinct aspects of leukocyte
sinusoids, including PECAM-1 (CD31); the mannose receptor, trafficking: (1) leukocyte entry into tissues from the circulation; (2)
which interacts with L-selectin; and common lymphatic endothelial migration within tissues; and (3) exit from tissues. Migration of
and vascular endothelial receptor 1 (CLEVER-1). 255 leukocytes throughout the body is essential for the development of
We still have very limited information about the signals that lymphocyte subsets and underpins their functions in immune sur-
determine the dwell time of lymphocytes in secondary lymphoid veillance and responses of effective adaptive immunity. The molecu-
organs (~12–24 hours for T cells). However, the recent observation lar reactions involved in leukocyte migration are tightly regulated
that the egress of both T and B cells from LNs can be prevented by and involve chemoattractants and adhesion molecules. Leukocyte
the immunosuppressant molecule FTY720 has revealed some of the migration is characterized by a considerable plasticity and specific-
principal mechanisms underlying lymphocyte egress. FTY720 is a ity, because different leukocyte subsets express unique patterns of
synthetic derivative of myriocin, a metabolite of the fungus Isaria sin- traffic molecules that enable their navigation into and within target
clairii, which has been used in Chinese traditional medicine. FTY720 tissues. Our expanding knowledge of the mechanisms that control
induces lymphocyte sequestration in LNs and causes profound lym- leukocyte trafficking will likely influence the development of multi-
phopenia. In animal models of transplantation and autoimmunity ple therapeutic strategies, including the use of stem cells, cell immu-
FTY720 causes immunosuppression, and it has recently been shown notherapy of cancer, and autoimmune, inflammatory, and infectious
to exert significant therapeutic effects in a placebo-controlled clini- diseases.
cal trial of relapsing multiple sclerosis. 256–258 Although lymphocyte
sequestration in LNs and lymphopenia in response to FTY720 have
been reported some time ago, the underlying molecular mechanisms SUGGESTED READINGS
114
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thymus). 262,263 Reports using FTY720 and S1P 1 -selective agonists extended family of chemokine receptors and introducing a new nomen-
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