The impact of variation in the number of CD8(+) T-cell precursors on the outcome of virus infection.
Ehl S., Klenerman P., Zinkernagel RM., Bocharov G.
We investigated the role of varying the initial number of naive antiviral CTL precursors on the dynamics of LCMV-DOCILE infection. C57BL/6 mice, exhibiting LCMV-specific CTLp frequencies of about 50, are protected against virus persistence over a range of infectious doses up to 10(4) pfu. With 10-fold higher doses, a 100-fold increase in CTLp is required to restore virus control. With doses above 10(6) pfu, elevation of the initial CTLp number leads only to lethal immunopathology. Similarly, a 1000-fold increase in the number of initial naïve CTLp enhances the overall kinetics of virus elimination, but cannot limit early virus spread within the first 48 h after low-dose infection (500 pfu). Increases in initial naïve virus-specific CTLp numbers are of limited benefit in antiviral control. In addition to the number of virus-specific T cells, the time period needed to reach cytolytic effector function is a limiting parameter.