Abstract
Malaria infection has long been associated with diminished T cell responses in vitro and more recently in experimental studies in vivo. Suppression of T cell-proliferative responses during malaria has been attributed to macrophages in a variety of murine and human systems. More recently, however, attention has been directed at the role of dendritic cells in this phenomenon, with several studies suggesting that maturation of dendritic cells is inhibited in vitro by the presence of malaria-infected E. In the studies reported here, we have examined the function of dendritic cells taken directly from infected mice. We found that they express high levels of costimulatory proteins and class II MHC, can activate naive T cells to produce IL-2 as efficiently as dendritic cells from uninfected mice, and support high levels of IFN-gamma production by naive T cells through an IL-12-dependent mechanism. Dendritic cells from infected mice also support higher levels of TNF-alpha production by naive T cells. These same dendritic cells present parasite Ag to a malaria-specific T cell hybridoma, a finding that demonstrates that dendritic cells participate in the generation of Ag-specific immunity during infection. Our findings challenge the contention that dendritic cell function is inhibited by malaria infection.
Publication types
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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 / immunology*
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Antigens, CD / metabolism
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Antigens, Protozoan / immunology
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Antigens, Protozoan / metabolism
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B7-1 Antigen / biosynthesis
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B7-2 Antigen
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CD11b Antigen / biosynthesis
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CD11c Antigen / biosynthesis
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CD40 Antigens / biosynthesis
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Cell Differentiation / immunology
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Cell Separation
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Cells, Cultured
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Dendritic Cells / parasitology
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Female
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Flow Cytometry
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Interferon-gamma / biosynthesis
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Interleukin-12 / physiology
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / biosynthesis
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Interphase / immunology
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Lymphocyte Activation
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Malaria / immunology*
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Malaria / parasitology
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Male
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Plasmodium yoelii / immunology
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Spleen / cytology
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Spleen / immunology
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Spleen / parasitology
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Spleen / pathology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Tumor Necrosis Factor-alpha / biosynthesis
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Up-Regulation / immunology
Substances
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Antigens, CD
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Antigens, Protozoan
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B7-1 Antigen
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B7-2 Antigen
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CD11b Antigen
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CD11c Antigen
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CD40 Antigens
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Cd86 protein, mouse
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Interleukin-2
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Membrane Glycoproteins
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Tumor Necrosis Factor-alpha
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Interleukin-12
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Interferon-gamma