Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural CD4+CD25+ regulatory T cells in vivo.
Repeated exposures to both microbial and innocuous Ags in vivo have been reported to both eliminate and tolerize T cells after their initial activation and expansion. The remaining tolerant T cells have been shown to suppress the response of naive T cells in vitro. This feature is reminiscent of natural CD4(+)CD25(+) regulatory T cells. However, it is not known whether the regulatory function of in vivo-tolerized T cells is similar to the function of natural CD4(+)CD25(+) regulatory T cells. In this study, we demonstrate that CD4(+)CD25(+) as well as CD4(+)CD25(-) T cells isolated from mice treated with superantigen three consecutive times to induce tolerance were functionally comparable to natural CD4(+)CD25(+) regulatory T cells, albeit more potent. The different subpopulations of in vivo-tolerized CD4(+) T cells efficiently down-modulated costimulatory molecules on dendritic cells, and their suppressive functions were strictly cell contact dependent. Importantly, we demonstrate that conventional CD4(+)CD25(-) T cells could also be induced to acquire regulatory functions by the same regimen in the absence of natural regulatory T cells in vivo, but that such regulatory cells were functionally different.
Grundström
Susanna
S
Active Biotech Research AB, Lund, Sweden.
Cederbom
Lukas
L
Sundstedt
Anette
A
Scheipers
Peter
P
Ivars
Fredrik
F
D000069594:Abatacept; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004334:Drug Administration Schedule; D004768:Enterotoxins / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D018796:Immunoconjugates; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage* / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D018796:Immunoconjugates; C499308:Rag2 protein, mouse; D015375:Receptors, Interleukin-2; D018089:Superantigens; D016212:Transforming Growth Factor beta; C064655:V(D)J recombination activating protein 2; D016753:Interleukin-10; C026066:enterotoxin A, Staphylococcal; D000069594:Abatacept; D017493:Leukocyte Common Antigens