Abstract
CD1d-restricted T-cells are activated by glycolipids presented by the major histocompatibility complex class-Ib molecule CD1d, found on the surface of antigen-presenting cells (APC). This interaction between APC, most notably dendritic cells (DC), and CD1d-restricted T-cells is an important regulatory step in the initiation of adaptive immune responses. It is well known that DC play a crucial role in the induction of contact hypersensitivity (CHS), a frequently studied form of in vivo T-cell-mediated immunity. In this study, we show that CD1d-restricted T-cells are also necessary for CHS, because both wild-type mice treated systemically or topically with CD1d glycolipid antagonists and CD1d-restricted T-cell-null mice have markedly diminished CHS responses. Thus, pharmacologic antagonists of CD1d can be used as effective inhibitors of CHS, a prototype for a variety of delayed-type tissue hypersensitivity responses.
Publication types
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Research Support, N.I.H., Extramural
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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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Administration, Topical
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Animals
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Antigen Presentation
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Antigens, CD1 / metabolism
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Antigens, CD1 / physiology*
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Antigens, CD1d
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Cell Line
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Dendritic Cells / cytology
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Dermatitis / pathology
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Dermatitis, Contact / metabolism*
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Dose-Response Relationship, Drug
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Glycolipids / chemistry
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Hypersensitivity
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Killer Cells, Natural / cytology*
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Killer Cells, Natural / metabolism
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Major Histocompatibility Complex
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Mutation
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Oxazolone / chemistry
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Oxazolone / pharmacology
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Phosphatidylethanolamines / pharmacology
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Polyethylene Glycols / pharmacology
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Receptors, Antigen, T-Cell / chemistry
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Receptors, Antigen, T-Cell / metabolism
Substances
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Antigens, CD1
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Antigens, CD1d
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DPPE-PEG2000
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Glycolipids
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Phosphatidylethanolamines
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Receptors, Antigen, T-Cell
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Oxazolone
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Polyethylene Glycols