Dynamic interaction between CD4+ T cells and parasitic helminths: mathematical models of heterogeneity in outcome

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Abstract
SUMMARY Potential mechanisms of immunoregulation have been investigated for the capacity to generate heterogeneity in the outcome of infection with helminth parasites. We have developed a mathematical model of the interaction between T cell and parasite populations, based on the assumption that activation of a Th1 CD4+ T cell response is required for host resistance. Antigen dose-dependent inhibition of Th1 cell proliferation generates heterogeneity in the outcome of host response to infection, with relatively low levels of exposure inducing resistance, and high levels of exposure associated with host susceptibility. Heterogeneity is additionally predicted in the duration of infection before individuals of the resistant class clear infection, with infection becoming more prolonged as the level of exposure rises. Similar categories of response are predicted if an alternative regulatory mechanism, that of interferon γ-regulated control of Th1 cell differentiation, is substituted into the model. However, the relationship between level of exposure and duration of infection is reversed. Results are discussed in the context of how these simple models of parasite–immune system interactions might be used to make predictions concerning specific examples of parasitic infection.