Abstract
The mechanism of CD40 ligand (CD40L)-mediated in vivo activation of CD4(+) T cells was examined by investigation of the development of experimental allergic encephalomyelitis (EAE) in CD40L-deficient mice that carried a transgenic T cell receptor specific for myelin basic protein. These mice failed to develop EAE after priming with antigen, and CD4(+) T cells remained quiescent and produced no interferon-gamma (IFN-gamma). T cells were primed to make IFN-gamma and induce EAE by providing these mice with B7.1(+) antigen-presenting cells (APCs). Thus, CD40L is required to induce costimulatory activity on APCs for in vivo activation of CD4(+) T cells to produce IFN-gamma and to evoke autoimmunity.
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology*
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Antigens, CD / biosynthesis
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B7-1 Antigen / biosynthesis
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B7-1 Antigen / immunology
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B7-2 Antigen
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Brain / immunology
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Brain / pathology
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CD4-Positive T-Lymphocytes / immunology*
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CD40 Ligand
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Interferon-gamma / biosynthesis
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Interleukin-4 / biosynthesis
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Lymphocyte Activation*
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / immunology*
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Mice
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Mice, Transgenic
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Myelin Basic Protein / immunology
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Receptors, Antigen, T-Cell / immunology
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Spinal Cord / immunology
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Spinal Cord / pathology
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Up-Regulation
Substances
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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Cd86 protein, mouse
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Membrane Glycoproteins
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Myelin Basic Protein
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Receptors, Antigen, T-Cell
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CD40 Ligand
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Interleukin-4
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Interferon-gamma