Abstract
CD4+CD25+ regulatory T cells (Treg) are potent immunosuppressive cells that are pivotal in the regulation of peripheral tolerance. In this report, we identify granzyme B (GZ-B) as one of the key components of Treg-mediated suppression. Induction of regulatory activity is correlated with the up-regulation of GZ-B expression. Proof of a functional involvement of GZ-B in contact-mediated suppression by Treg is shown by the reduced ability of Treg from GZ-B-/- mice to suppress as efficiently as Treg from WT mice. GZ-B-mediated suppression is perforin independent, because suppression by Treg from perforin-/- and WT is indistinguishable. Additionally, suppression mediated by Treg appears to be mediated, in part, by the induction of apoptosis in the CD4+CD25- effector cell. In summary, GZ-B is one of the key mechanisms through which CD4+CD25+ Treg induce cell contact-mediated suppression.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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CD4-Positive T-Lymphocytes / enzymology
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CD4-Positive T-Lymphocytes / immunology
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Cell Communication / genetics
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Cell Communication / immunology*
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Cells, Cultured
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Coculture Techniques
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Glucocorticoid-Induced TNFR-Related Protein
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Granzymes
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Immune Sera / pharmacology
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Immunosuppression Therapy / methods
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Perforin
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Pore Forming Cytotoxic Proteins
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Receptors, Interleukin-2 / biosynthesis*
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Receptors, Nerve Growth Factor / immunology
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Receptors, Nerve Growth Factor / physiology
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor / physiology
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Serine Endopeptidases / deficiency
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Serine Endopeptidases / genetics
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Serine Endopeptidases / physiology*
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Serine Proteinase Inhibitors / pharmacology
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / enzymology*
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T-Lymphocytes, Regulatory / immunology*
Substances
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Glucocorticoid-Induced TNFR-Related Protein
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Immune Sera
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Membrane Glycoproteins
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Pore Forming Cytotoxic Proteins
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Receptors, Interleukin-2
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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Serine Proteinase Inhibitors
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Tnfrsf18 protein, mouse
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Perforin
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Granzymes
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Gzmb protein, mouse
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Serine Endopeptidases