Regulation of Primary Cytotoxic Response by Antigen-Presenting Cells

Abstract:-- Cytotoxic CD8 T lymphocytes (CTL) represent a major immune mechanism used by animals to defend themselves against viruses and intracellular parasites. We predict organization of primary CTL response by comparing 34 mathematical models with kinetic data reported for two persisting viruses, lymphocytic choreomeningitis virus (LCMV) and simian immunodeficiency virus (SIV, closely related to HIV). We make the hypothesis that both viruses impair CTL response in the same way, by infecting macrophages or dendritic cells (APC). We fit the models to data on 4 representative strains of LCMV in mice, some of which show doze-dependent behavior, and one strain of SIV in 4 rhesus macaques. Our best model has 13 fitting parameters and includes 9 time-dependent variables corresponding to six CTL compartments and three APC compartments. In agreement with our hypothesis, best-fitting parameters vary between LCMV and SIV, between individual monkeys, and between LCMV strains within the same range, one decimal order