Abstract
The B7 family of cell surface molecules expressed on APC provides accessory signals to T cells via either CD28 or CTLA-4. However, while CD28 transduces a costimulatory signal that is required for an optimal immune response, CTLA-4 transmits a negative signal. These studies use an anti-CTLA-4 mAb to directly address the role of this T cell surface molecule in experimental allergic encephalomyelitis (EAE). CTLA-4 regulation of disease was assessed during initial immune cell interactions and during the effector stage of the encephalitogenic immune response. The effects of anti-CTLA-4 treatment were schedule dependent. CTLA-4 blockade during the onset of clinical symptoms markedly exacerbated disease, enhancing mortality. Disease exacerbation was associated with enhanced production of the encephalitogenic cytokines TNF-alpha, IFN-gamma and IL-2. Hence, CTLA-4 regulates the intensity of the autoimmune response in EAE, attenuating inflammatory cytokine production and clinical disease manifestations.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Abatacept
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Animals
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Antibodies, Monoclonal / pharmacology*
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Antigens, CD / physiology
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Antigens, Differentiation / physiology*
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Autoimmune Diseases / immunology*
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B7-1 Antigen / physiology
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B7-2 Antigen
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CD28 Antigens / physiology*
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CTLA-4 Antigen
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Cytokines / biosynthesis*
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Female
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Humans
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Immunoconjugates*
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Interferon-gamma / biosynthesis
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Interleukin-2 / biosynthesis
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Membrane Glycoproteins / physiology
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Mice
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Rats
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Signal Transduction / drug effects
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T-Lymphocytes, Cytotoxic / immunology*
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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B7-1 Antigen
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B7-2 Antigen
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CD28 Antigens
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CD86 protein, human
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CTLA-4 Antigen
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CTLA4 protein, human
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Cd86 protein, mouse
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Cd86 protein, rat
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Ctla4 protein, mouse
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Ctla4 protein, rat
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Cytokines
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Immunoconjugates
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Interleukin-2
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Membrane Glycoproteins
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Tumor Necrosis Factor-alpha
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Abatacept
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Interferon-gamma