Plasmacytoid dendritic cells are thought to act as sentinels in early defense against viral infection on the basis of their expression of TLRs and the intracellular nucleic acid-sensing RIG-I-like helicases, and their high production of antiviral type I interferons (see Sections 3-10 and 3-22). For several reasons, they are not thought to be involved in a major way in the antigen-specific activation of naive T cells. Plasmacytoid dendritic cells express fewer MHC class II and co-stimulatory molecules on their surface, and they process antigens less efficiently than conventional dendritic cells. In addition, unlike conventional dendritic cells, plasmacytoid dendritic cells do not cease the synthesis and recycling of MHC class II molecules after being activated. This means that they rapidly recycle their surface MHC II molecules and so cannot present pathogen-derived peptide:MHC complexes to T cells for extended periods, as conventional dendritic cells do.
Plasmacytoid dendritic cells may, however, act as helper cells for antigen presentation by conventional dendritic cells. This activity was revealed by studies in mice infected with the intracellular bacterium Listeria monocytogenes. Normally, IL-12 made by conventional dendritic cells induces CD4 T cells to produce abundant IFN-γ, which helps macrophages kill the bacteria. When plasmacytoid dendritic cells were experimentally eliminated, IL-12 production by conventional dendritic cells decreased, and the mice became susceptible to Listeria. It appears that plasmacytoid dendritic cells interact with conventional dendritic cells to sustain IL-12 production. Activation of plasmacytoid dendritic cells through TLR-9 induces the expression of CD40 ligand (CD40L or CD154), a TNF-family transmembrane cytokine, which binds to CD40, a TNF-family receptor that is expressed by activated conventional dendritic cells. This interaction enables conventional dendritic cells to sustain production of the pro-inflammatory cytokine IL-12, strengthening the IL-12-induced production of IFN-γ by T cells. Plasmacytoid dendritic cells can also produce IL-12 themselves, although in smaller amounts than conventional dendritic cells do.
9-12 Macrophages are scavenger cells that can be induced by pathogens to present foreign antigens to naive T cells.
The two other cell types that can act as antigen-presenting cells to T cells are macrophages and B cells, although there is an important distinction between the function of antigen presentation by these cells and that of dendritic cells. It is unlikely that macrophages and B cells present antigen to activate naive T cells. Rather, these cells present antigen to T cells that have already been primed by conventional dendritic cells as a means to recruit the effector, or ‘helper,’ functions of T cells that, in turn, provide signals to enhance their own effector functions. In this way, naive B cells that are activated by antigen bound to their surface immunoglobulin receptor present peptides derived from that antigen to elicit help from effector T cells in order to differentiate into immunoglobulin-secreting cells. And, as we learned in Chapter 3, while many microorganisms that enter the body are engulfed and destroyed by phagocytes, which provide an innate, antigen-nonspecific first line of defense against infection, some pathogens have developed mechanisms to avoid elimination by innate immunity, such as resisting the killing properties of phagocytes. Macrophages that have ingested microorganisms but have failed to destroy them can use antigen presentation to recruit the adaptive immune response to enhance their microbicidal activities, as we will discuss further in Chapter 11.