Abstract
Costimulation mediated by the interactions of the B7 Ags (CD80/CD86) on APC with CD28 on the responding T cell regulates the magnitude of the immune response and may influence Th1/Th2 development. The IL-12Rbeta2 subunit plays a critical role in maintaining IL-12 responsiveness and controlling Th1 lineage commitment. We demonstrate that IL-2 and IL-12 resulting from CD28/B7 interactions both play a critical role in the induction of expression of the IL-12Rbeta2 subunit and as a result the differentiation of pathogenic autoreactive effector cells. These findings suggest that targeting IL-2 and IL-12 simultaneously may be effective in the treatment of Th1-mediated autoimmunity.
MeSH terms
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Abatacept
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Adjuvants, Immunologic / physiology
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Animals
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Antigens, CD
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Antigens, Differentiation / pharmacology
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B7-1 Antigen / physiology*
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CD28 Antigens / genetics
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CD28 Antigens / physiology*
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CD40 Antigens / metabolism
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CD40 Ligand
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CTLA-4 Antigen
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Cell Differentiation / immunology
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Encephalomyelitis, Autoimmune, Experimental / etiology
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Immunoconjugates*
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Interferon-gamma / biosynthesis
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Interleukin-12 / biosynthesis*
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Interleukin-12 / pharmacology
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Interleukin-12 / physiology
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Interleukin-2 / physiology
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Ligands
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Mice, Transgenic
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Receptors, Interleukin / biosynthesis*
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Receptors, Interleukin / physiology
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Receptors, Interleukin-12
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Signal Transduction / immunology*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
Substances
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Adjuvants, Immunologic
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Antigens, CD
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Antigens, Differentiation
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B7-1 Antigen
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CD28 Antigens
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CD40 Antigens
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CTLA-4 Antigen
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Ctla4 protein, mouse
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Immunoconjugates
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Interleukin-2
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Ligands
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Membrane Glycoproteins
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Receptors, Interleukin
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Receptors, Interleukin-12
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CD40 Ligand
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Interleukin-12
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Abatacept
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Interferon-gamma