Page 402 - Veterinary Immunology, 10th Edition

have proven to be highly effective anticancer drugs [Chapter 35].)
VetBooks.ir It takes 48 to 72 hours after T cell CD154 binds to CD40 before the
Resting antigen-presenting cells express neither CD80 nor CD86.

antigen-presenting cells begin to express CD80/86 and the T cells

express CTLA-4. CD80 and CD86 can bind to either CD28 or CTLA-
4. However, because CTLA-4 binds these molecules with a higher
affinity than does CD28, the inhibitory effect of CTLA-4 gradually
predominates. When CTLA-4 binds to CD80 on antigen-presenting

cells, it induces the production of indoleamine dioxygenase (IDO),
an enzyme that destroys tryptophan. In the absence of this amino
acid, T cells cannot respond to antigen, and so the T cell response is
terminated (Chapter 20).

Co-Stimulatory Cytokines

Cytokines, as described in Chapter 8, are proteins that regulate
immune cell functions. Antigen-presenting cells are major sources

of these cytokines. Antigen-presenting cells may be triggered to
produce cytokines by many different stimuli. These include
microbial PAMPs binding to TLRs, as well as T cells signaling
through CD40 and CD154. As described in Chapter 10, different
dendritic cell populations secrete different cytokine mixtures. These

mixtures in turn determine the nature of the helper T cell response.
For example, IL-12 from cDC1 cells promotes the differentiation of
Th1 cells. Further differentiation is promoted by IFN-γ and IL-18. In

the absence of IL-12, T cells differentiate into Th2 cells and their
further differentiation is promoted by IL-33, -25, -4, -13, and TSLP.
Classical type 2 dendritic cells (cDC2) and macrophages stimulated
through TLR2 secrete IL-23. This cytokine, together with IL-6 and
transforming growth factor-β (TGF-β), results in the development

of Th17 cells (Fig. 14.8).

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