Abstract
Transforming growth factor (TGF)-beta exerts a counter-regulatory effect on interleukin (IL)-12-mediated immune modulation. The underlying mechanism is not fully understood. Here we demonstrate that the expression of IL-12Rbeta1 and IL-12Rbeta2 in MBP peptide Ac1-11-primed splenocytes is upregulated upon antigen stimulation. TGF-beta induces an unresponsiveness of these primed splenocytes to IL-12 signaling through a mechanism involved in inhibition of both IL-12Rbeta1 and beta2. The modulation of IL-12Rbeta1 and beta2 expression by Ac1-11 stimulation and TGF-beta is mainly involved in CD4+ population. These data indicate that both IL-12Rbeta1 and IL-12Rbeta2 expression are crucial during T cell activation. TGF-beta-induced inhibition of IL-12R expression will reduce cellular immune responses during IL-12-mediated autoimmune disease.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Autoantigens / immunology
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Autoimmune Diseases / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Female
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Gene Expression Regulation / drug effects
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology
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Interleukin-12 / antagonists & inhibitors*
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Interleukin-12 / immunology
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred Strains
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Myelin Basic Protein / immunology*
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Peptide Fragments / immunology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Interleukin / antagonists & inhibitors*
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Receptors, Interleukin / genetics
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-12
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Spleen / immunology
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Transforming Growth Factor beta / antagonists & inhibitors
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Transforming Growth Factor beta / immunology
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Transforming Growth Factor beta / pharmacology*
Substances
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Autoantigens
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Il12rb1 protein, mouse
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Il12rb2 protein, mouse
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Myelin Basic Protein
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Peptide Fragments
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RNA, Messenger
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Receptors, Interleukin
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Receptors, Interleukin-12
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Transforming Growth Factor beta
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Interleukin-12
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Interferon-gamma