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FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number of circulating mature lymphocytes by acceleration of lymphocyte homing
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First demonstration that FTY720 sequesters lymphocytes from blood and spleen into LN and PP.
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Chiba K., Yanagawa Y., Masubuchi Y., Kataoka H., Kawaguchi T., Ohtsuki M., Hoshino Y. FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number of circulating mature lymphocytes by acceleration of lymphocyte homing. J Immunol. 160:1998;5037-5044. First demonstration that FTY720 sequesters lymphocytes from blood and spleen into LN and PP.
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Demonstration that FTY720 does not impair T cell activation, expansion and memory in response to systemic infection, and that the drug does not delay viral clearance. First demonstration that FTY720 has potential to inhibit autoimmunity against islet cells.
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Pinschewer D.D., Ochsenbein A.F., Odermatt B., Brinkmann V., Hengartner H., Zinkernagel R.M. FTY720 immunosuppression impairs effector T-cell peripheral homing without affecting induction, expansion, and memory. J Immunol. 164:2000;5761-5770. Demonstration that FTY720 does not impair T cell activation, expansion and memory in response to systemic infection, and that the drug does not delay viral clearance. First demonstration that FTY720 has potential to inhibit autoimmunity against islet cells.
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Demonstration that FTY720 is a substrate of SK1a, and is phosphorylated by lymphoid tissue explants, and that the phosphorylated form is a potent agonist at four S1P receptors. The agonistic signal alters the intrinsic mobility of cells and alters lymphocyte traffic, but does not lead to apoptosis. First evidence that FTY720 is highly effective in models of human multiple sclerosis.
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Brinkmann V., Davis M.D., Heise C.E., Albert R., Cottens S., Hof R., Bruns C., Prieschl E., Baumruker T., Hiestand P., et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 277:2002;21453-21457. Demonstration that FTY720 is a substrate of SK1a, and is phosphorylated by lymphoid tissue explants, and that the phosphorylated form is a potent agonist at four S1P receptors. The agonistic signal alters the intrinsic mobility of cells and alters lymphocyte traffic, but does not lead to apoptosis. First evidence that FTY720 is highly effective in models of human multiple sclerosis.
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Demonstration that FTY720 is phosphorylated in vivo and that S1P receptor agonists including FTY720-P empty lymphoid sinuses by retention of lymphocytes on the abluminal side of the SLE, thereby inhibiting egress to lymph.
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Mandala S., Hajdu R., Bergstrom J., Quackenbush E., Xie J., Milligan J., Thornton R., Shei G.J., Card D., Keohane C., et al. Alteration of lymphocyte trafficking by sphingosine 1-phosphate receptor agonists. Science. 296:2002;346-349. Demonstration that FTY720 is phosphorylated in vivo and that S1P receptor agonists including FTY720-P empty lymphoid sinuses by retention of lymphocytes on the abluminal side of the SLE, thereby inhibiting egress to lymph.
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Fu F., Hu S., Deleo J., Li S., Hopf C., Hoover J., Wang S., Brinkmann V., Lake P., Shi V. Longterm islet graft survival in STZ and autoimmune induced diabetes models by immunosuppressive and potential insulinotropic agent FTY720. Transplantation. 73:2002;1425-1430.
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Demonstration that the protective effect of FTY720 after transplantation of allogeneic skin correlates with a reduced infiltration of T cells into the transplant.
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