Interactions with other cells
Irrespective of where DCs are located, be it in tissues, in transit or in lymphoid organs, they constantly communicate with other cells either by direct touch and/or hands-free with soluble cytokines. In this way DCs can influence a wide range of cells but can also be influenced. It is difficult to determine which cell in a particular pair has the louder voice in some of these conversations, but sometimes the function of a DC changes as a result of the interaction.
In tissues we know that many cells can induce DC maturation for example eosinophils, epithelial cells, mast cells and activated macrophages. Mast cells and activated macrophages not only activate DCs but can also alter the level of IL-12 that the mature DC secretes in nearby lymph nodes later on. The activated macrophage influences the DC to keep secreting IL-12 whereas the histamine released by the mast cells has the opposite effect and reduces the level of IL-12. Both immature and mature DCs are able to activate nearby resting NK cells in tissues. NK cells then signal back to DCs by both direct touch and cytokines and make the DCs secrete IL-12. Activated NK cells are on the other hand less helpful and kill immature DCs in the tissues using the death inducing ligand TRAIL. In doing this, NK cells edit out DCs that could potentially drive anti-self reactions. Mature DCs are protected from NK cell assassination as they have high levels of surface MHC class I molecules which turns the NK cells off.
In lymphoid organs mature DCs not only initiate signals in antigen specific naive T cells, but also receive back-talk from the T cell through CD40L on the T cell and CD40 on the DC. This enhances the power of the DC to activate T cells. DCs also “hold hands” with T cells that have immunosuppressive capacity called T regulatory cells and these cells can slow down DC maturation and prevent them from interacting with other autoreactive T cells.
When DCs and B cells talk in the lymph nodes, the main outcome of the conversation is B cell maturation to antibody producing plasma cells. B cells can only respond to intact antigen using the BCR, which DCs can accommodate by carrying intact antigens from the tissue to the B cells in the lymph node via one of their Fc receptors or via another surface molecules called DC-SIGN. It is not yet determined if the B cells are able to change DC function as a result of this interaction. Do all of these cell interactions make DCs central to an immune response?