Abstract
Induction of OVA-specific CTL by cross-priming requires help from CD4 T cells, which use CD154 to signal CD40 on the APC. To further dissect the molecular pathways involved in cross-priming, we examined the role of Rel, an NF-kappaB family member. c-rel(-/-) mice failed to generate OVA-specific CTL by cross-priming, but could induce CTL to HSV-1. Using chimeric mice, Rel expression was shown to be required by the APC, but not by the T cells. Notably, the deficiency in Rel could be overcome by triggering CD40, implying that the APC required Rel before receipt of the CD40 signal. These data suggest that the cross-priming APC must receive two signals before it can stimulate CTL. The first signal is Rel dependent and is required before activation of CD4 helper T cells, which then deliver the second signal using CD154 to trigger CD40.
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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Antigen Presentation / genetics
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Antigen-Presenting Cells / cytology
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Antigen-Presenting Cells / immunology*
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Antigen-Presenting Cells / metabolism*
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Antigens, Viral / administration & dosage
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CD40 Antigens / physiology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cytotoxicity, Immunologic* / genetics
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Epitopes, T-Lymphocyte / immunology
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Herpesvirus 1, Human / immunology
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Injections, Intravenous
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Lymphocyte Activation* / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Ovalbumin / immunology
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Proto-Oncogene Proteins c-rel / biosynthesis
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Proto-Oncogene Proteins c-rel / deficiency
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Proto-Oncogene Proteins c-rel / genetics
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Proto-Oncogene Proteins c-rel / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocytes, Cytotoxic / immunology*
Substances
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Antigens, Viral
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CD40 Antigens
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Epitopes, T-Lymphocyte
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Proto-Oncogene Proteins c-rel
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Ovalbumin