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. 1998 Dec;95(4):591–594. doi: 10.1046/j.1365-2567.1998.00639.x

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.

Y Yanagawa 1, Y Masubuchi 1, K Chiba 1
PMCID: PMC1364357  PMID: 9893050

Abstract

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.

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Selected References

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  1. Berlin C., Berg E. L., Briskin M. J., Andrew D. P., Kilshaw P. J., Holzmann B., Weissman I. L., Hamann A., Butcher E. C. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993 Jul 16;74(1):185–195. doi: 10.1016/0092-8674(93)90305-a. [DOI] [PubMed] [Google Scholar]
  2. Brandtzaeg P. Overview of the mucosal immune system. Curr Top Microbiol Immunol. 1989;146:13–25. doi: 10.1007/978-3-642-74529-4_2. [DOI] [PubMed] [Google Scholar]
  3. Butcher E. C., Picker L. J. Lymphocyte homing and homeostasis. Science. 1996 Apr 5;272(5258):60–66. doi: 10.1126/science.272.5258.60. [DOI] [PubMed] [Google Scholar]
  4. Chiba K., Hoshino Y., Suzuki C., Masubuchi Y., Yanagawa Y., Ohtsuki M., Sasaki S., Fujita T. FTY720, a novel immunosuppressant possessing unique mechanisms. I. Prolongation of skin allograft survival and synergistic effect in combination with cyclosporine in rats. Transplant Proc. 1996 Apr;28(2):1056–1059. [PubMed] [Google Scholar]
  5. 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. 1998 May 15;160(10):5037–5044. [PubMed] [Google Scholar]
  6. Ford W. L., Gowans J. L. The traffic of lymphocytes. Semin Hematol. 1969 Jan;6(1):67–83. [PubMed] [Google Scholar]
  7. Fujita T., Hirose R., Yoneta M., Sasaki S., Inoue K., Kiuchi M., Hirase S., Chiba K., Sakamoto H., Arita M. Potent immunosuppressants, 2-alkyl-2-aminopropane-1,3-diols. J Med Chem. 1996 Oct 25;39(22):4451–4459. doi: 10.1021/jm960391l. [DOI] [PubMed] [Google Scholar]
  8. Hamann A., Andrew D. P., Jablonski-Westrich D., Holzmann B., Butcher E. C. Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol. 1994 Apr 1;152(7):3282–3293. [PubMed] [Google Scholar]
  9. Hoshino Y., Suzuki C., Ohtsuki M., Masubuchi Y., Amano Y., Chiba K. FTY720, a novel immunosuppressant possessing unique mechanisms. II. Long-term graft survival induction in rat heterotopic cardiac allografts and synergistic effect in combination with cyclosporine A. Transplant Proc. 1996 Apr;28(2):1060–1061. [PubMed] [Google Scholar]
  10. Issekutz T. B. Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by the TA-2 monoclonal antibody. A likely role for VLA-4 in vivo. J Immunol. 1991 Dec 15;147(12):4178–4184. [PubMed] [Google Scholar]
  11. Kawaguchi T., Hoshino Y., Rahman F., Amano Y., Higashi H., Kataoka H., Ohtsuki M., Teshima K., Chiba K., Kakefuda T. FTY720, a novel immunosuppressant possessing unique mechanisms. III. Synergistic prolongation of canine renal allograft survival in combination with cyclosporine A. Transplant Proc. 1996 Apr;28(2):1062–1063. [PubMed] [Google Scholar]
  12. Lasky L. A., Singer M. S., Dowbenko D., Imai Y., Henzel W. J., Grimley C., Fennie C., Gillett N., Watson S. R., Rosen S. D. An endothelial ligand for L-selectin is a novel mucin-like molecule. Cell. 1992 Jun 12;69(6):927–938. doi: 10.1016/0092-8674(92)90612-g. [DOI] [PubMed] [Google Scholar]
  13. Martin D. R., Miller R. G. In vivo administration of histoincompatible lymphocytes leads to rapid functional deletion of cytotoxic T lymphocyte precursors. J Exp Med. 1989 Sep 1;170(3):679–690. doi: 10.1084/jem.170.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ngan J., Kind L. S. Suppressor T cells for IgE and IgG in Peyer's patches of mice made tolerant by the oral administration of ovalbumin. J Immunol. 1978 Mar;120(3):861–865. [PubMed] [Google Scholar]
  15. Steeber D. A., Green N. E., Sato S., Tedder T. F. Lyphocyte migration in L-selectin-deficient mice. Altered subset migration and aging of the immune system. J Immunol. 1996 Aug 1;157(3):1096–1106. [PubMed] [Google Scholar]
  16. Suzuki S., Enosawa S., Kakefuda T., Amemiya H., Hoshino Y., Chiba K. Long-term graft acceptance in allografted rats and dogs by treatment with a novel immunosuppressant, FTY720. Transplant Proc. 1996 Jun;28(3):1375–1376. [PubMed] [Google Scholar]
  17. Suzuki S., Enosawa S., Kakefuda T., Shinomiya T., Amari M., Naoe S., Hoshino Y., Chiba K. A novel immunosuppressant, FTY720, with a unique mechanism of action, induces long-term graft acceptance in rat and dog allotransplantation. Transplantation. 1996 Jan 27;61(2):200–205. doi: 10.1097/00007890-199601270-00006. [DOI] [PubMed] [Google Scholar]
  18. Tamatani T., Kitamura F., Kuida K., Shirao M., Mochizuki M., Suematsu M., Schmid-Schönbein G. W., Watanabe K., Tsurufuji S., Miyasaka M. Characterization of rat LECAM-1 (L-selectin) by the use of monoclonal antibodies and evidence for the presence of soluble LECAM-1 in rat sera. Eur J Immunol. 1993 Sep;23(9):2181–2188. doi: 10.1002/eji.1830230920. [DOI] [PubMed] [Google Scholar]
  19. Tamatani T., Kotani M., Miyasaka M. Characterization of the rat leukocyte integrin, CD11/CD18, by the use of LFA-1 subunit-specific monoclonal antibodies. Eur J Immunol. 1991 Mar;21(3):627–633. doi: 10.1002/eji.1830210314. [DOI] [PubMed] [Google Scholar]
  20. Tanaka T., Masuko T., Yagita H., Tamura T., Hashimoto Y. Characterization of a CD3-like rat T cell surface antigen recognized by a monoclonal antibody. J Immunol. 1989 Apr 15;142(8):2791–2795. [PubMed] [Google Scholar]
  21. Yanagawa Y., Sugahara K., Kataoka H., Kawaguchi T., Masubuchi Y., Chiba K. FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. II. FTY720 prolongs skin allograft survival by decreasing T cell infiltration into grafts but not cytokine production in vivo. J Immunol. 1998 Jun 1;160(11):5493–5499. [PubMed] [Google Scholar]

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