Dendritic cells and the eye: their role in the ocular immune response

Published on May 5, 2014   51 min

Other Talks in the Series: Cells of the Innate Immune System

0:00
This is a Henry Stewart talk, and I'm John Forrester from the University of Aberdeen, Scotland. My presentation is on dendritic cells in the eye and their role in the ocular immune response.
0:13
Dendritic cells were discovered by Ralph Steinman in 1973. Steinman and Cohn reported this in the Journal of Experimental Medicine of a novel cell type in the peripheral lymphoid organs of mice. Later Ralph Steinman identified these as the most potent antigen presenting cells promoting the adaptive immune response. And he also later identified them, in fact, as having a major role in homeostasis of the immune response by promoting non-responsiveness to immune stimulation, i.e. tolerance. For this work he had international recognition in 2007 with the Lasker Award, and most recently has been awarded the Nobel Prize for this work.
1:01
The ontogeny of dendritic cells is interesting. They arise as hematopoietic precursors as stem cells in the bone marrow. And the lineage of these, of course, is to produce macrophages and a subset of myeloid dendritic cells called, conventional dendritic cells. There is also a smaller population of CD34 myeloid precursor cells which enter the bloodstream, and these may produce a subset of cells called the plasmacytoid dendritic cells. There has been a suggestion that this other cell type, the plasmacytoid dendritic cell, may also arise from a lymphoid precursor. But it's generally believed that in fact, this is not correct, and most of this small subset of dendritic cells arises from the bone marrow. Whether or not the plasmacytoid dendritic cell has a separate lineage from the conventional dendritic cell is unclear, but they certainly do appear to have specific and selective transcription factors, such as the E2-2 transcription factor, which is, in the absence of this, the possibility that the plasmacytoid dendritic cell can revert to a conventional dendritic cell might arise.
2:18
Dendritic cells are characterized by their surface phenotype. Several different cell types: the CD8 positive dendritic cell, CD4 positive dendritic cell, the CD4-CD8 negative dendritic cell, Langerhans cells, dermal interstitial dendritic cells, and as mentioned, the plasmacytoid dendritic cell. Almost all of these cells have the definition of the CD11c marker, apart from the plasmacytoid dendritic cell, where the expression of this marker is rather low.
2:51
Most recently, however, it's been realized that there is a myeloid precursor cell leading to a myeloid dendritic precursor cell. The expression of Flt3 ligands leads to the predendritic cells and the plasmacytoid dendritic cells, leading to the conventional dendritic cells in the periphery, and as I've mentioned, the plasmacytoid dendritic cells, which as I've also mentioned may have the possibility to reconvert to a conventional dendritic cell. There is also this macrophage dendritic cell, MDP precursor cell, which under, the influence of all the macrophage colony stimulating factor, can induce the monocytic cell line, which can become these inflammatory dendritic cells, otherwise known as TipDC's because of their ability to produce TNFα and other cytokines.
3:48
So in essence, there are several phenotypic and characteristic features of the dendritic cell subtypes. In the bone marrow, GM-CSF is the essential cytokine for the induction of dendritic cells. They express the Flt3 receptor. And there are no lymphoid DCs in the bone marrow. Lymphoid DCs are CD8α DEC-205 positive cells. And there are also CD8α negative 33D1 positive cells in the spleen. I'll discuss these later. In the lymph nodes there are several subsets of dendritic cells, as indicated on the slide here. DEC-205 positive, CD8α positive, CD8α negative, CD11b positive myeloid dendritic cells, and the migratory dendritic cells, some of which express Langerin, and the CD11c intermediate. In the skin there are Langerhans cells, of course, as well-recognized for many years, and some of these are Langerin positive, while others are Langerin negative, particularly those in the sub-population of dermal DCs. In the intestines, CD103 seems to be an important surface phenotypic marker for Peyer's patch DCs. And in the lamina propria there are CD103 positive and CD103 negative dendritic cells. The CD103 positive CD11b negative cell is the equivalent of the DEC205 positive spleen dendritic cell. All of this has been reviewed in detail by Liu and Nussenzweig in Immunological Reviews, 2010.
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Dendritic cells and the eye: their role in the ocular immune response

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