Page 574 - Veterinary Immunology, 10th Edition
P. 574
VetBooks.ir Effector T Cell Memory
In contrast to the prolonged antibody response, the effector phase
of T cell responses is relatively brief. Indeed, cytotoxicity is seen
only in the presence of antigen. This is logical. Sustained cytotoxic
activities or overproduction of cytokines could cause severe tissue
damage.
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Naïve CD8 T cells are long-lived resting cells that continuously
recirculate between the bloodstream and lymphoid organs. Once
they encounter antigen, they multiply rapidly in an effort to keep
pace with the growth of invading pathogens. They reach a peak 5 to
7 days after infection when pathogen-specific, cytotoxic T cells can
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make up 50% to 70% of the total CD8 T cells. As with other
lymphocytes, asymmetric division results in two daughter cells
with different fates. In the case of CD8+ cells it results in the
generation of effector and memory effector T cells. The effector cells
are derived from the daughter cell closest to the antigen-presenting
cell. The memory T cells are derived from the daughter distal to the
APC. The proximal cell has increased glycolytic activity and
increased expression of effector molecules. The distal cell has
increased lipid metabolism, increased expression of anti-apoptotic
molecules, and lives very much longer.
Once the infection has cleared, most of the effector cells are
superfluous. Therefore up to 95% of them undergo apoptosis 1 to 2
weeks after infection. Elimination of these excess T cells is a tightly
controlled process involving the CD95 pathway.
The number of surviving memory cells is directly related to the
intensity of the primary response. In general only 5% to 10% of the
peak number of cytotoxic T cells survive as memory T cells.
Survival may be a function of duration of exposure to antigen. Cells
exposed to antigen for prolonged periods may die, whereas cells
exposed only briefly may live. The observation that chronic viral
infections can exhaust T cells and impair both cytotoxicity and
memory is consistent with this idea.
Memory T cells can be distinguished from naïve T cells by their
phenotype, by secreting a different mixture of cytokines, and by
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their behavior. For example, memory T cells are CD44 and express
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