Page 563 - Veterinary Immunology, 10th Edition

VetBooks.ir Cytotoxic T Cell Subsets

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Subsets of CD8 T cells have been identified in rodents, where they
are called Tc1 and Tc2. Tc1 cells secrete IL-2 and IFN-γ, whereas

Tc2 cells secrete IL-4 and IL-5. A third subset, Tc0, has an
unrestricted cytokine profile. Unlike helper cells that can
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differentiate readily into Th1 or Th2 cells, CD8 T cells show a
strong preference for the Tc1 phenotype. Differentiation into Tc2
requires exposure to large amounts of IL-4. All three subsets are

cytotoxic.
As described in Chapter 14, T cell interactions with their targets
are regulated by positive co-stimulation from CD28 and negative

signals from CTLA-4. In some cancers, where T cell cytotoxicity is
insufficient to kill the cancer cells, blockage of CTLA-4 by
monoclonal antibodies will enhance T cell cytotoxicity and induce
long-term tumor remission.
Another molecule that limits T cell cytotoxicity is called

programmed cell death-1 (PD-1, CD279). This is a T cell receptor
that binds to ligands (PD-L1 and PD-L2) on target cells and then
inhibits signaling from the TCR. Upregulation of PD-1 is a normal

consequence of T cell activation and is required to terminate an
immune response. Persistent viral infections and some cancers
induce strong stable expression of PD-1 on activated T cells. This
leads to T cell exhaustion, failure of activation, and a loss of T cell
function. When PD-L1 is expressed on tumor cells, it protects them

from attack by cytotoxic T cells. Conversely, inhibition of PD-1
signaling will enhance T cell–mediated destruction of certain
cancers. Both CTLA-4 and PD-1 are regarded as immune

checkpoint molecules and their inhibition by monoclonal antibodies
may result in successful cancer treatments. You can read more
about these checkpoint inhibitors in Chapter 35.

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