Abstract
Classical and plasmacytoid dendritic cells (DC) play important roles in the defense against murine and human infections with herpes simplex virus (HSV). So far, CD8α expression has only been reported for murine DC. CD8α+ DC have prominent cross-presenting activities, which are enhanced by murine CD8α+ PDC. The human orthologue of murine CD8α+ DC, the CD141 (BDCA3)+ DC, mainly cross-present after TLR3 ligation. We report here the serendipitous finding that a subset of human PDC upregulates CD8α upon HSV-1 stimulation, as shown by gene array and flow cytometry analyses. CD8α, not CD8ß, was expressed upon exposure. Markers of activation, migration, and costimulation were upregulated on CD8α-expressing human PDC. In these cells, increased cytokine and chemokine levels were detected that enhance development and function of T, B, and NK cells, and recruit immature DC, monocytes, and Th1 cells, respectively. Altogether, human CD8α+ PDC exhibit a highly activated phenotype and appear to recruit other immune cells to the site of inflammation. Further studies will show whether CD8α-expressing PDC contribute to antigen cross-presentation, which may be important for immune defenses against HSV infections in vitro and in vivo.
Highlights
Since Ralph Steinman first described a new subset of cells characterized by tree-like processes in 1973 (Steinman and Cohn, 1973), knowledge about dendritic cells (DC) in mice and humans has grown exponentially
IFN-α and IL-6 enhance T cell, B cell, and NK cell development and function; IL-8 recruits T cells and induces their degranulation; IL-1RA inhibits IL-1 induced T cell activation, and the chemokines MIP-1α, MIP-1β, and MCP1 recruit immature DC, monocytes, and Th1 cells. These data indicate that a subset of plasmacytoid dendritic cells (PDC) gradually upregulates a homodimeric CD8α receptor upon herpes simplex virus (HSV)-1 stimulation, exposes a highly activated phenotype, and appears to be active in recruiting other immune cells to the site of inflammation. This is—at least to our knowledge—the first report that a subset of human PDC is capable of expressing CD8α at the cell surface upon herpes simplex virus type 1 (HSV-1) stimulation
This subset is phenotypically different from the CD8α– PDC in expressing increased levels of markers for activation, costimulation, and migration
Summary
Since Ralph Steinman first described a new subset of cells characterized by tree-like processes in 1973 (Steinman and Cohn, 1973), knowledge about dendritic cells (DC) in mice and humans has grown exponentially. We report here the serendipitous finding that a subset of human PDC upregulates CD8α upon HSV-1 stimulation, as shown by gene array and flow cytometry analyses. Human HSV-exposed PDC express CD8α likely—tumor-associated antigens, evidence is lacking that CD8 expression plays any role in the development and function of these cells (Shortman and Heath, 2010).
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