Differential effects of single dose FTY720 on CD62L+ B-cells in stable renal allograft recipients.
FTY720, a sphingosine-1-phosphate receptor agonist, is the archeotype of a new class of immune modulators, which redirects lymphocytes from the peripheral blood into secondary lymphatic tissue. Previously, it was shown that FTY720 differentially decreases peripheral T-cells, expressing specific chemokine and adhesion receptors. Here, we investigated the effect of single doses FTY720 on peripheral B-cells expressing CD62L, CD11a, CD49d and CXCR4 in stable human renal allograft recipients. Peripheral blood lymphocytes were isolated by Ficoll density centrifugation and stained with monoclonal antibodies against CD3 or CD19 and CD62L, CD11a, CD49d, CXCR4 to determine the percentage of these T- and B-cell subpopulations. Total lymphocyte counts were measured by routine laboratory diagnostics to calculate absolute lymphocyte subset counts. In FTY720 treated patients, total lymphocyte counts decreased by 31.8% (0.25-2 mg) and 60.4% (3.5 mg), and total T-cell counts by 38.8% (0.25-2 mg) and 70.9% (3.5 mg). In comparison, total B-cell counts decreased by 32.2% (0.25-2 mg) and 61.1% (3.5 mg). The reduction of CD62L+ B-cells was less pronounced as compared to CD62L+ T-cells (0.25-2 mg: 15.7% vs. 57.3%; 3.5 mg: 57.2% vs. 86.9%). CD11a+ B-cells decreased by 15.4% (0.25-2 mg) and 57.1% (3.5 mg), and CD49d+ B-cells by 15.0% (0.25-2 mg) and 56.7% (3.5 mg). CXCR4+ B-cells decreased by 19.9% (0.25-2 mg) and 57.2% (3.5 mg). In vitro experiments showed that FTY720 did not change the mean expression of CD62L, CD11a, CD49d and CXCR4 on CD19+ B-cells. In conclusion FTY720 treatment reduces B-cells expressing CD62L to a significant lesser degree than T-cells expressing CD62L.
Böhler
Torsten
T
Department of Internal Medicine-Nephrology, Charité Campus Mitte, Humboldt-University, Berlin, Germany. Boehlert@toulouse.inserm.fr
Schütz
Manuela
M
Budde
Klemens
K
Neumayer
Hans-H
HH
Waiser
Johannes
J
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D040881:CD11a Antigen / Q000276:immunology; D004311:Double-Blind Method; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D039441:Integrin alpha4 / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology; D011409:Propylene Glycols / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000819:agonists; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D040881:CD11a Antigen; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D019718:Receptors, CXCR4; D049349:Receptors, Lysosphingolipid; D019041:L-Selectin; D039441:Integrin alpha4; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine