FTY720 treatment of kidney transplant patients: a differential effect on B cells, naïve T cells, memory T cells and NK cells.
FTY720 alters lymphocyte recirculation and homing by interfering with S1P receptors on lymphocytes, possibly in combination with chemokine receptors, and induces a decrease in PBL counts. In fresh, whole blood samples of 14 kidney transplant patients, we analyzed by flow cytometry the effect of FTY on the number of NK cells, monocytes, naïve (CCR7+) T cells, memory (CCR5+) T cells and B cells. Patients treated with 0.5, 2.5 or 5mg FTY/day showed a strong decrease in T and B cell numbers. NK cells and monocytes were not affected. FTY reduced primarily naïve T cells. From the memory T cells (CCR5+), predominantly CD8 cells, 40-60% remained in the circulation. The majority of the CCR7+ cells disappeared from the circulation within 3-6h, while a further reduction was achieved later. The more slowly decrease in naïve CCR7+ T cell numbers was also observed in the group treated with 0.25mg FTY/day. Elispot assays revealed no IL-4 producing cells and a low frequency of IFN-gamma producing cells. We suggest that both CCR7 dependent and independent mechanisms are involved in the depletion of T cells from peripheral blood.
Vaessen
Leonard M B
LM
Department of Internal Medicine-Transplantation, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, Room Ee559, P.O. Box 1738, NL-3000 DR Rotterdam, The Netherlands.
van Besouw
Nicole M
NM
Mol
Wendy M
WM
Ijzermans
Jan N M
JN
Weimar
Willem
W
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D000068876:Fingolimod Hydrochloride; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D019713:Receptors, CCR5 / Q000276:immunology; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
C515370:CCR7 protein, human; C515187:CXCR3 protein, human; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D000068876:Fingolimod Hydrochloride; D009173:Mycophenolic Acid; D013110:Sphingosine