Fig. 11.26 Generation of memory T cells expansion phase of 6 days after infection. When the infection is eliminated, after an infection. After an infection, in this case with an attenuated strain of Listeria
LLOp:I-Ab+ 106 106 cells 105 105 104 104 103 103 102 102 101 monocytogenes, the number of T cells specific for the listeriolysin (LLO) toxin increases dramatically and then falls back to give a sustained low level of memory T cells. T-cell responses are detected by binding of an MHC tetramer consisting of an LLO peptide bound by I-Ab. The left panel shows the primary response of CD4 T cells that are LLO-specific, and the right panel shows the contraction and memory phase. Approximately 100 T cells in the naive T-cell repertoire expand to about 100,000 effector cells by day 7, and then contract to about 7000 memory cells by day 25. These memory cells then slowly decay to 500 cells by day 450. Data courtesy of Marc Jenkins.
a slower contraction phase follows in which these T cells are reduced by about 100-fold within a few weeks. This leaves a population of memory T cells present at a frequency of about 10-fold higher than in the naive repertoire, and this population persists with a half-life of about 60 days.
11-21 Memory T cells arise from effector T cells that maintain sensitivity to IL-7 or IL-15.
Naive and memory T cells can be distinguished by differences in their expression of various cell-surface proteins, by their distinct responses to stimuli, and by their expression of certain genes. Overall, memory cells continue to express many markers of activated T cells, such as phagocytic glycoprotein-1 (Pgp1, CD44), but they stop expressing other activation markers, such as CD69. Memory T cells express more Bcl-2, a protein that promotes cell survival and may be responsible for their long half-life. Figure 11.27 lists several molecules by which naive, effector, and memory T cells can be distinguished.
Fig. 11.27 Expression of many proteins alters when naive T cells become memory T cells. Proteins that are expressed differently in naive T cells, effector T cells, and memory T cells include adhesion molecules, which govern interactions with antigen-presenting cells and endothelial cells; chemokine receptors, which affect migration to lymphoid tissues and sites of inflammation; proteins and receptors that promote the survival of memory cells; and proteins that are involved in effector functions, such as granzyme B. Some changes also increase the sensitivity of the memory T cell to antigen stimulation. Many of the changes that occur in memory T cells are also seen in effector cells, but some, such as expression of the cell-surface proteins CD25 and CD69, are specific to effector T cells; others, such as expression of the survival factor Bcl-2, are limited to long-lived memory T cells. This list represents a general picture that applies to both CD4 and CD8 T cells in mice and humans, but some details that may differ between these sets of cells have been omitted for simplicity.
Days after transfer 1470 0 Mice infected with LCMV generate a primary CD8 response; some effector cells express high levels of IL-7R˜, while others do not Only transfer of the IL-7R˜hi-CD8 T cells into naive mice led to robust expansion of antigen-specifc CD8 cells after secondary challenge LCMV TCR-transgenic mouse naive mice antigen challenge Number of antigen-specifcCD8 T cells antigen challenge CD8 IL-7R˜hi cells transfer transfer IL-7R˜lo cells