Sphingosine-1-phosphate Receptor Agonism Impairs the Efficiency of the Local Immune Response by Altering Trafficking of Naive and Antigen-Activated CD4+ T Cells
作者： Jenny H. Xie , Naomi Nomura , Sam L. Koprak , Elizabeth J. Quackenbush , Michael J. Forrest
DOI: 10.4049/JIMMUNOL.170.7.3662
关键词: ZAP70 、 CD28 、 Interleukin 21 、 Immunology 、 Cell biology 、 Biology 、 Cytotoxic T cell 、 T cell 、 Antigen-presenting cell 、 IL-2 receptor 、 Immune system
摘要: FTY720 (2-amino-[2-(4-octylphenyl) ethyl]-1,3-propanediol hydrochloride) is an immunosuppressive agent that inhibits allograft rejection. We recently demonstrated FTY-phosphate, the active metabolite of FTY720, acts as a full agonist for sphingosine-1-phosphate (S1P) receptors. Furthermore, activation S1P receptors with their natural ligand, S1P, well pharmacological ligands leads to lymphopenia, probably due sequestration lymphocytes in secondary lymphoid organs. In present study we used local Ag-challenged mouse model examine effects on T cell draining lymph node (DLN) and release activated cells peripheral blood compartment. showed number Ag-activated CD4+ DLN after injection Ag CFA into footpad was dramatically reduced treatment. However, proliferation, both vitro vivo, not impaired by FTY720. Our results suggest efficiency responses response defective recirculation naive caused found numbers mice were equally treatment, suggesting subsets are sequestered DLNs. Thus, induces immunosuppression through inhibition from
jimmunol.org参考文章(24)
K Chiba, H Higashi, Y Amano, H Kataoka, F Rahman, M Ohtsuki, K Teshima, T Kawaguchi, Y Hoshino, S Suzuki, T Kakefuda, FTY720, a novel immunosuppressant possessing unique mechanisms. III. Synergistic prolongation of canine renal allograft survival in combination with cyclosporine A International congress for xenotransplantation. ,vol. 28, pp. 1062- 1063 ,(1996)
Chiba K, Masubuchi Y, Suzuki C, Ohtsuki M, Fujita T, Yanagawa Y, Sasaki S, Hoshino Y, FTY720, a novel immunosuppressant possessing unique mechanisms. I. Prolongation of skin allograft survival and synergistic effect in combination with cyclosporine in rats. International congress for xenotransplantation. ,vol. 28, pp. 1056- 1059 ,(1996)
Yukitoshi Nagahara, Masahiko Ikekita, Takahisa Shinomiya, Immunosuppressant FTY720 induces apoptosis by direct induction of permeability transition and release of cytochrome c from mitochondria. Journal of Immunology. ,vol. 165, pp. 3250- 3259 ,(2000) , 10.4049/JIMMUNOL.165.6.3250
Kenji Chiba, Kunio Sugahara, Yoshiki Yanagawa, Hirotoshi Kataoka, Takafumi Kawaguchi, Yumi Masubuchi, 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 Journal of Immunology. ,vol. 160, pp. 5493- 5499 ,(1998)
Daniel D. Pinschewer, Adrian F. Ochsenbein, Bernhard Odermatt, Volker Brinkmann, Hans Hengartner, Rolf M. Zinkernagel, FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. Journal of Immunology. ,vol. 164, pp. 5761- 5770 ,(2000) , 10.4049/JIMMUNOL.164.11.5761
Kenji Chiba, Yoshiki Yanagawa, Makio Ohtsuki, Hirotoshi Kataoka, Takafumi Kawaguchi, Yukio Hoshino, Yumi Masubuchi, 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 Journal of Immunology. ,vol. 160, pp. 5037- 5044 ,(1998)
Jonathan Kaye, Mei-Ling Hsu, Marie-Elizabeth Sauron, Stephen C. Jameson, Nicholas R. J. Gascoigne, Stephen M. Hedrick, Selective development of CD4 + T cells in transgenic mice expressing a class II MHC-restricted antigen receptor Nature. ,vol. 341, pp. 746- 749 ,(1989) , 10.1038/341746A0
Mamoru Matsuura, Tomonori Imayoshi, Takeki Okumoto, Effect of FTY720, a novel immunosuppressant, on adjuvant- and collagen-induced arthritis in rats. International Journal of Immunopharmacology. ,vol. 22, pp. 323- 331 ,(2000) , 10.1016/S0192-0561(99)00088-0
Seiichi Suzuki, Shin Enosawa, Toshihiro Kakefuda, Xiao-Kang Li, Makoto Mitsusada, Shiro Takahara, Hiroshi Amemiya, Immunosuppressive effect of a new drug, FTY720, on lymphocyte responses in vitro and cardiac allograft survival in rats Transplant Immunology. ,vol. 4, pp. 252- 255 ,(1996) , 10.1016/S0966-3274(96)80026-8
Makoto Mitsusada, S. Suzuki, Eiji Kobayashi, Shin Enosawa, Toshihiro Kakefuda, Michio Miyata, Prevention of graft rejection and graft-versus-host reaction by a novel immunosuppressant, FTY720, in rat small bowel transplantation. Transplant International. ,vol. 10, pp. 343- 349 ,(1997) , 10.1007/S001470050068