How Does Cross-Reactive Stimulation Affect the Longevity of CD8+ T Cell Memory?
Figure 2
Simulations of the Change in Memory following Exposure to Pathogens
In the left panels we follow the change in size of representative memory clones shown in different colors (the thicker blue line represents many clones together). We mark the average decline in memory per exposure, d, defined as a decline in the total number of cells in memory lineages that were occupied prior to exposure to the pathogen, normalized to the total number of memory cells. In the right panels we show the frequency distribution of the size of these lineages at the beginning (open bars) and end (filled bars) of the simulation. We consider 75 exposures to new pathogens.
(A) We set cross-reactivity to zero.
(B) Memory lineages have the same average cross-reactivity, but we assume there is no competition between the expansions of cells in different lineages.
(C) Memory lineages have the same average cross-reactivity, and we add competition for expansion as described in the text.
(D) Memory lineages have different levels of cross-reactivity (but keep the average cross-reactivity unchanged), and there is no competition for expansion.
Parameters are as in Table 2 with on average 50 naive and 10 memory lineages specific for each pathogen (i.e., f = 5 · 10−5 and g = 2 · 10−3).
(A) We set g = 0 and let naive cells expand 200-fold, resulting in the expansion factor m = 2·107/106 × 200 = 4·103. The total expansion of naïve cells is M = 50m = 2 · 105.
(B) We let naive cells expand 200-fold and memory 2-fold (i.e., c = 1).
(C) The total expansion is kept the same as in (A), T = 2 · 105, but there is competition between the expansion of naive and memory cells as described in the text.
(D) Cross-reactivity is log-normally distributed, resulting in ḡ ≈ 2 · 10−3 and variance , for 5 · 103 memory clones.