The impact of variation in the number of CD8(+) T-cell precursors on the outcome of virus infection.
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.
Ehl
S
S
Department of Pathology, University of Zurich, Zurich, CH-8091, Switzerland. STEPHANEHL@AOL.COM
Klenerman
P
P
Zinkernagel
R M
RM
Bocharov
G
G
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000517:prevention & control / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017735:Virus Latency