Immunomodulatory drug FTY720 induces regulatory CD4(+)CD25(+) T cells in vitro.
As a novel immunosuppressant, FTY720 (2-amino-2-(2-[4-octylphenyl] ethyl)-1, 3-propanediol hydrochloride) has been used to prevent the allograft rejection in organ transplantation. FTY720 can prolong markedly survival of the allograft by inducing apoptosis of reactive lymphocytes and by redirecting the homing of lymphocytes. However, as the archetype of a new class of immune modulators, the potential effect of FTY720 on the immune response needs to be elucidated further. In this study, FTY720 was added into the mixed lymphocyte reaction (MLR) consisting of murine splenocytes from BALB/c and C57BL/6, to observe its direct effect on the induction of CD4(+)CD25(+) regulatory T cells. It was demonstrated that the proportion of CD4(+)CD25(+) and CD4(+)CD25(+)forkhead box P3 (FoxP3)(+) T cells in MLR were increased significantly by FTY720 treatment, and the expression of FoxP3 mRNA in lymphocytes was also enhanced markedly by the drug. A synergetic effect was observed between FTY720 and co-stimulation blockades. Moreover, analysis of the function of FTY720-treated cells manifested an increased suppressive activity in an in vitro antigen-specific proliferation assay. In conclusion, FTY720 can increase the number and enhance the functional activity of CD4(+)CD25(+) regulatory T cells in MLR, and these FTY720-treated cells possess the activity to down-regulate the alloreactivity of lymphocytes, indicating its potential use for therapeutic purposes.
Zhou
P J
PJ
Division of Kidney Transplantation, Department of Urology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
Wang
H
H
Shi
G H
GH
Wang
X H
XH
Shen
Z J
ZJ
Xu
D
D
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics; D007155:Immunologic Factors / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011409:Propylene Glycols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015415:Biomarkers; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007155:Immunologic Factors; D053645:Interleukin-2 Receptor alpha Subunit; D011409:Propylene Glycols; D012333:RNA, Messenger; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine