Dendritic cell
Dendritic cells constitute a group of cells diverse in terms of ontogeny and tissue localisation. We will mainly cover the so-called “conventional” myeloid dendritic cells.
They are the only cells that can carry out the cross-presentation . They are also the only cells capable of activating naive T cells.
As such, they are the pivot between innate and adaptive immunity, an essential actor of the immune reaction. They are the leader of professional antigen-presenting cells.
Attention to “false friends”: do not confuse dendritic cells and follicular dendritic cells
Follicular dendritic cells have this name because they are cells with large cytoplasmic extensions, located within lymphoid follicles.
Although they have the same name as dendritic cells, their role and characteristics are very different.
- They are not the product of haematopoiesis, but come from stromal cells.
- They do not present antigen for the activation of T cells.
On the other hand, they interact very closely with B cells (they are involved in particular in their maturation and differentiation) and therefore play an important role in the T-dependent humoral immune response.
Haematopoiesis / cytology
Dendritic cells are very heterogeneous in origin and purpose. Although most have haematopoietic progenitors, they are virtually absent from the bloodstream because they reside primarily in secondary lymphoid organs. We distinguish between:
Myeloid dendritic cells (so-called conventional)
- Migratory
They are the archetype of dendritic cells. Naïve, they reside in tissues with a cytoplasm typically displaying dendrites, but a morphology which will vary from one tissue to another. They are then sensitive to danger signals and capable of phagocytising antigens before migrating to secondary lymphoid organs, where they present the antigen to naive T cells.
- Residents of secondary lymphoid organs
They have the same morphological and cytometric characteristics as the previous ones, but are sedentary in the secondary lymphoid organs where they collect and present antigens.
Plasmacytoid dendritic cells
Plasmacytoid dendritic cells are circulating, round cells in their basal state. After activation, they acquire a phenotype of conventional dendritic cells, and can therefore present the antigen (most often viral) then produce a large quantity of pro-inflammatory cytokines.
Functions
They have distinct functions depending on their state of maturation, which correlates with their location.
Immature dendritic cells ensure antigen uptake
Dendritic cells are then sentinel cells, which:
- are recruited by cytokines and chemokines produced by inflammatory tissues.
- recognise danger signals (MAMP and DAMP) by innate immunity receptors called PRRs, intracellular or expressed on the surface of the cell.
- capture the antigen by three different endocytosis mechanisms:
Once the antigen has been captured, the maturation process is initiated.
Dendritic cells mediate antigen presentation to T cells
Dendritic cells are specialised in antigen presentation.
They have Class I HLA molecules in the same way as all nucleated cells and platelets. They have the particularity – shared with all so-called professional antigen-presenting cells – of possessing Class II HLA molecules allowing the presentation of exogenous antigens.
Dendritic cells are the only cells capable of cross-presentation, i.e. of presenting exogenous peptides via Class I HLA molecules.
Mature dendritic cells mediate activation of naive T cells
Depending on the cellular interactions and the cytokine environment at the inflammatory site, the dendritic cell acquires a new phenotype capable of activating naive T cells and inducing different types of T response. This new phenotype is characterised by very high expression. This new phenotype is characterised by very high expression.
- of HLA molecules to present the antigen to T cells,
- of co-stimulation molecules (CD80, CD86, CD40) to enable the activation of T cells,
- and of CCR7 leading to the migration of dendritic cells towards the lymph nodes (place of concentration of naive T cells).
Mature dendritic cells secrete cytokines which will direct the T-cell response
In addition to antigen recognition, T cell activation requires cytokine signals to be complete (see T cell activation)
What needs to be remembered
Dendritic cell is an essential actor in immunity.It is the only one able to activate naive T cells, and as such, it is the pivot between innate and adaptive immunity. It is also the only one able to carry out cross-presentation, that is to say prepare exogenous antigens in Class I HLA molecules, and therefore activate CD8+ T cells to induce a cellular reaction towards antigens not expressed in the recipient’s dendritic cell.
Cross-presentation is also useful outside of transplantation, to induce cellular immunity against intracellular pathogens that do not usually infect dendritic cells or against tumour cells.
