FTY720 causes lymphocytes to get trapped in nodes (bracket).

Rosen/AAAS

Organ rejection in transplant patients can be prevented using the drug FTY720, but the drug's mechanism of action has been unknown. Now, Suzanne Mandala, Hugh Rosen, and colleagues (Merck Research Laboratories, Rahway, NJ) show that it acts by retaining lymphocytes in lymph nodes, preventing their circulation through the bloodstream.

B and T lymphocytes are either retained in lymph nodes in order to contact antigens and antigen-presenting cells or sent back out into the bloodstream for circulation. Circulating lymphocytes may enter tissues, where they mediate protective activities or cause tissue damage. Most immunosuppressive drugs work by inhibiting lymphocyte function: they either kill the cells directly, inhibit their production, or block signals downstream of antigen recognition. But FTY720 works in a novel manner.

Rosen's group found that a phosphate ester metabolite of FTY720 mimics the natural lipid...

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