Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Abatacept
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Animals
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Antigens, CD
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Antigens, Differentiation / biosynthesis
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CTLA-4 Antigen
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Cell Communication / genetics
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Cell Communication / immunology
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Cells, Cultured
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Clonal Anergy / genetics
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Clonal Anergy / immunology
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Clonal Deletion / genetics
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Clonal Deletion / immunology
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Cytokines / physiology
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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Dose-Response Relationship, Immunologic
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Drug Administration Schedule
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Enterotoxins / administration & dosage*
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Enterotoxins / pharmacology
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Female
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Genes, T-Cell Receptor beta / immunology
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Immunity, Innate / genetics
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Immunoconjugates*
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Injections, Intravenous
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Interleukin-10 / antagonists & inhibitors
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Interleukin-10 / metabolism
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Leukocyte Common Antigens / biosynthesis
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, SCID
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Mice, Transgenic
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Receptors, Interleukin-2 / biosynthesis*
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Staphylococcus aureus / immunology
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Superantigens / administration & dosage*
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Superantigens / pharmacology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Transforming Growth Factor beta / antagonists & inhibitors
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / physiology
Substances
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Antigens, CD
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Antigens, Differentiation
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CTLA-4 Antigen
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Ctla4 protein, mouse
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Cytokines
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DNA-Binding Proteins
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Enterotoxins
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Immunoconjugates
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Rag2 protein, mouse
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Receptors, Interleukin-2
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Superantigens
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Transforming Growth Factor beta
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V(D)J recombination activating protein 2
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Interleukin-10
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enterotoxin A, Staphylococcal
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Abatacept
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Leukocyte Common Antigens