THE IMPACT OF VARIATION IN THE NUMBER OF CD8(-CELL PRECURSORS ON THE OUTCOME OF VIRUS-INFECTION() T)

We investigated the role of varying the initial number of naive antivi ral CTL precursors on the dynamics of LCMV-DOCILE infection, C57BL/6 m ice, exhibiting LCMV-specific CTLp frequencies of about 50, are protec ted against virus persistence over a range of infectious doses up to 1 0(4) pfu, With 10-fold higher doses, a 100-fold increase in CTLp is re quired to restore virus control. With doses above 10(6) pfu, elevation of the initial CTLp number leads only to lethal immunopathology. Simi larly, a 1000-fold increase in the number of initial naive CTLp enhanc es the overall kinetics of virus elimination, but cannot limit early v irus spread within the first 48 h after low-dose infection (500 pfu), Increases in initial naive virus-specific CTLp numbers are of limited benefit in antiviral control. In addition to the number of virus-speci fic T cells, the time period needed to reach cytolytic effector functi on is a limiting parameter. (C) 1998 Academic Press.