FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats, III. Increase in frequency of CD62L-positive T cells in Peyer's patches by FTY720-induced lymphocyte homing.
FTY720, a novel immunosuppressant, sequesters circulating mature lymphocytes, especially T cells, within lymph nodes and Peyer's patches by accelerating lymphocyte homing, and thereby causes lymphocyte depletion in the blood. The FTY720-induced acceleration of lymphocyte homing appears to be mediated by lymphocyte homing receptors including CD62L, CD49d/beta7, and CD11a/CD18. In this study, expressions of CD62L, CD49d and CD11a on T cells in the peripheral blood, lymph nodes and Peyer's patches were analysed by flow cytometry in rats given FTY720 (1 mg/kg) orally. FTY720 markedly decreased the number of peripheral blood T cells, while not affecting CD62L, CD49d and CD11a expressions at 1-3 hr after administration. In contrast, both the frequency of CD62L-positive T cells and intensity of CD62L expression on T cells were increased in Peyer's patches but not lymph nodes at 3 hr after administration of FTY720. CD49d and CD11a expressions on T cells were unaffected by FTY720 in both Peyer's patches and lymph nodes at the same point in time. On the other hand, analysis of lymphocyte homing with calcein-labelled lymphocytes and anti-CD62L monoclonal antibody (mAb) confirmed that FTY720 predominantly increased CD62L-dependent lymphocyte homing to Peyer's patches. These findings indicate that FTY720 increases the frequency of CD62L-positive T cells by accelerating CD62L-predominant homing in Peyer's patches.
Yanagawa
Y
Y
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd, Iruma, Saitama, Japan.
Masubuchi
Y
Y
Chiba
K
K
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D039423:Integrin alpha1; D019041:L-Selectin / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D018655:Lymphocyte Count / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008297:Male; D010581:Peyer's Patches / Q000276:immunology*; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D007166:Immunosuppressive Agents; D039423:Integrin alpha1; D016169:Lymphocyte Function-Associated Antigen-1; D011409:Propylene Glycols; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine