Recruitment times, proliferation, and apoptosis rates during the CD8(+) T-Cell response to lymphocytic choriomeningitis virus

The specific CD8(+) T-cell response during acute lymphocytic choriomeningit is virus (LCMV) infection of mice is characterized by a rapid proliferation phase, followed by a rapid death phase and long-term memory. In BALB/c mic e the immunodominant and subdominant CDS' responses are directed against th e NP118 and GP283 epitopes. These responses differ mainly in the magnitude of the epitope-specific CDS' T-cell expansion. Using mathematical models to gether with a nonlinear parameter estimation procedure, we estimate the par ameters describing the rates of change during the three phases and thereby establish the differences between the responses to the two epitopes. We fin d that CDS' cell proliferation begins 1 to 2 days after infection and occur s at an average rate of 3 day(-1), reaching the maximum population size bet ween days 5 and 6 after immunization. The 10-fold difference in expansion t o the NP118 and GP283 epitopes can be accounted for in our model by a 3.5-f old difference in the antigen concentration of these epitopes at which T-ce ll stimulation is half-maximal. As a consequence of this 3.5-fold differenc e in the epitope concentration needed for T-cell stimulation, the rates of activation and proliferation of T cells specific for the two epitopes diffe r during the response and in combination can account for the large differen ce in the magnitude of the response. After the peak, during the death phase , the population declines at a rate of 0.5 day(-1), i.e., cells have an ave rage life time of 2 days. The model accounts for a memory cell population o f 5% of the peak population size by a reversal to memory of 1 to 2% of the activated cells per day during the death phase.