Fig. 4.

Mathematical modeling of memory T cell attrition by active, passive or both mechanisms: Tc memory clone dynamics during the primary and secondary response to cross-reacting viruses, under three models of attrition simulated by IMMSIM. Abscissa: time steps (TS) 0–1100. Ordinate: Tc memory clone cells numbers. Arrows at TS = 1 and TS = 500 indicate the time of inoculum of V1 (70 particles) and V2 (120 particles), respectively. V1 clearance is complete at TS ≅ 200 and V2 clearance at TS ≅ 700. Attrition is enacted in active by simulating IFN type 1 secretion by target epithelial cells at the time of the infection. The lymphokine diffuses locally and then causes the death of memory cells by contact, thus creating space for V2 specific cell growth. There is an early decrease in all memory clones; the cross-reacting ones show a typical “dip” before the secondary rise. Passive attrition is simulated by a drastic decrease of lifespan of memory cells when they reach a density threshold. It starts significantly later than active and its effect is felt for several hundreds TS, as it causes a characteristic decrease of the secondary clones after the secondary peak. The combination of both modes in both features early plunging of primary memory, a dip before the secondary growth and the after peak fall. The experiments shown also illustrate the significant findings of stimulation of new responding clones in active and both, and of favoring high affinity clones by active and both. This is epitomized by the relative behaviour of the green (low affinity for V1, medium affinity for V2) and the red (no reaction with V1, high affinity for V2) clones in the three attrition modes. By contrast note that clones blue and yellow have high affinity for V1 but do not bind V2, clones purple, lightblue and black do not bind V1 and have high affinity or medium affinity (black) for V2.