Physiological sphingosine 1-phosphate requirement for optimal activity of mouse CD4+ regulatory T Cells.
Sphingosine 1-phosphate (S1P) evokes T cell chemotaxis at 1-100 nM and inhibits chemotaxis to chemokines at 300 nM-1 uM through their predominant S1P1 G protein-coupled receptor (R). Mouse CD4+25+ regulatory T cells now are shown to express the same pattern of S1P1 > S1P4 >>other S1P Rs as other CD4 T cells. CD4+25+ T cell suppression of 3H-thymidine uptake and IL-2 generation by CD4+25- T cells stimulated with anti-T cell receptor antibodies without S1P was enhanced significantly by S1P at normal blood and lymph concentrations. These levels of S1P also enhanced IL-10 generation by CD4+25+ T cells by up to threefold compared with that without S1P but decreased IL-10 from CD4+25- T cells. That IL-10 from CD4+25+ T cells incubated with S1P mediates suppressive activity was demonstrated by prevention with neutralizing anti-IL-10 or anti-IL-10 receptor antibodies. Extracellular fluid S1P thus is required for optimal activity of CD4+25+ T cells.
Wang
Wengang
W
Department of Medicine, University of California, San Francisco, California 94143-0711, USA.
Graeler
Markus H
MH
Goetzl
Edward J
EJ
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D060908:CTLA-4 Antigen; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D049312:Receptors, Lysophospholipid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D008246:Lysophospholipids; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D015375:Receptors, Interleukin-2; D049312:Receptors, Lysophospholipid; D016753:Interleukin-10; C060506:sphingosine 1-phosphate; D013110:Sphingosine