Page 284 - Veterinary Immunology, 10th Edition

levels 100 times higher on mature DCs than on other cell types such
VetBooks.ir as B cells or macrophages. Their expression of costimulatory

molecules such as CD86 (Chapter 14) may also rise 100-fold.
Mature DCs are the only cells that can trigger a primary T cell

response. One reason for this is that mature DCs can assemble
complete T cell activation complexes (antigen-loaded MHC plus
costimulatory molecules) within the cell before they are carried to
the cell surface. Mature DCs also express DC-SIGN (CD209), a C-

type lectin that binds a ligand called intercellular adhesion
molecule-3 (ICAM-3 or CD50) on naïve T cells. DC-SIGN permits
transient binding between DCs and T cells. It allows a single
dendritic cell to rapidly screen thousands of T cells to find the few

that are expressing a compatible antigen receptor. Because of their
potency, only a few DCs are needed to trigger a strong T cell
response. Thus one dendritic cell may activate as many as 3000 T
cells.

Tolerance Induction

Under steady-state conditions, in the absence of inflammation or
infection, some immature DCs will spontaneously mature and
migrate to lymphoid tissues carrying normal tissue antigens on

their MHC molecules. If a T cell recognizes this “normal” antigen,
the T cell will undergo apoptosis and die. Alternatively, these DCs
may trigger the production of IL-10, a suppressive cytokine that

generates regulatory T cells. As a result, the processing of normal
tissue antigens or even harmless environmental antigens by DCs
can lead to T cell deletion and immunological tolerance (Chapter
20). In humans a subset of DCs secrete the immunosuppressive
molecule indoleamine 2,3-dioxygenase (IDO). This subset has a

regulatory function and may be able to promote tolerance. The
decision to induce either a tolerogenic response or a defensive
immune response likely depends upon the presence of microbial

PAMPs or tissue DAMPs. A good example of this is the tolerance
expressed in the intestine to food antigens and commensal bacteria.
DCs that sample these antigens are potent inducers of retinoic acid
and TGF-β (Chapter 21). This retinoic acid promotes the
differentiation of regulatory T cells and thus prevents the

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