Page 401 - Veterinary Immunology, 10th Edition

VetBooks.ir

FIG. 14.7 Antigen-presenting cells and helper T cells engage in a
dialog. Thus binding of antigen to the TCR causes the T cell to
express CD40 ligand (CD154). This engages CD40 on the antigen-
presenting cell. As a result, CD28 and CTLA-4 are expressed on
the T cell, and CD80 or CD86 is expressed on the antigen-
presenting cell. Depending on which receptors are engaged, the T
cell may be stimulated or suppressed.

CD28-CD80/CD86 Signaling

CD28, a receptor induced by CD40-CD154 signaling on T cells, has
two alternative ligands: either CD80 on dendritic cells,

macrophages, and activated B cells, or CD86 on B cells. When CD80
or CD86 bind to CD28, signals are generated that cause the T cell, in
turn, to express yet another receptor, CTLA-4 (also called CD152).
CTLA-4 may bind to either CD80 or CD86. The binding of CD28 to
its ligands amplifies the stimulus to the T cell eight-fold. CD28

stimulation enhances the production of IL-2 and other cytokines,
upregulates cell survival genes, promotes energy metabolism, and
facilitates T cell division. On the other hand, when CTLA-4 binds to

CD80 or CD86, T cell activation is suppressed. The balance between
these opposing signals delivered to T cells through these two
receptors, CD28 and CTLA-4, regulates the intensity of T cell
responses. (Inhibitors of CTLA-4 enhance T cell cytotoxicity and

401