Abstract
Type I IFNs are important for direct control of viral infection and generation of adaptive immune responses. Recently, direct stimulation of CD4(+) T cells via type I IFNR has been shown to be necessary for the formation of functional CD4(+) T cell responses. In contrast, we find that CD4(+) T cells do not require intrinsic type I IFN signals in response to combined TLR/anti-CD40 vaccination. Rather, the CD4 response is dependent on the expression of type I IFNR (IFNαR) on innate cells. Further, we find that dendritic cell (DC) expression of the TNF superfamily member OX40 ligand was dependent on type I IFN signaling in the DC, resulting in a reduced CD4(+) T cell response that could be substantially rescued by an agonistic Ab to the receptor OX40. Taken together, we show that the IFNαR dependence of the CD4(+) T cell response is accounted for exclusively by defects in DC activation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Female
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Interferon Type I / physiology*
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Mice
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Mice, 129 Strain
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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OX40 Ligand
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Radiation Chimera / immunology
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Receptor, Interferon alpha-beta / biosynthesis*
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Receptor, Interferon alpha-beta / deficiency
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Receptor, Interferon alpha-beta / genetics
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Tumor Necrosis Factors / biosynthesis*
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Tumor Necrosis Factors / genetics
Substances
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Ifnar1 protein, mouse
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Interferon Type I
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Membrane Glycoproteins
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OX40 Ligand
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Tnfsf4 protein, mouse
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Tumor Necrosis Factors
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Receptor, Interferon alpha-beta