Stable and transient periodic oscillations in a mathematical model for CTL response to HTLV-I infection.

London School of Economics-LSE, London, UK.
Journal of Mathematical Biology (Impact Factor: 2.37). 07/2011; 65(1):181-99. DOI: 10.1007/s00285-011-0455-z
Source: PubMed

ABSTRACT The cytotoxic T lymphocyte (CTL) response to the infection of CD4+ T cells by human T cell leukemia virus type I (HTLV-I) has previously been modelled using standard response functions, with relatively simple dynamical outcomes. In this paper, we investigate the consequences of a more general CTL response and show that a sigmoidal response function gives rise to complex behaviours previously unobserved. Multiple equilibria are shown to exist and none of the equilibria is a global attractor during the chronic infection phase. Coexistence of local attractors with their own basin of attractions is the norm. In addition, both stable and unstable periodic oscillations can be created through Hopf bifurcations. We show that transient periodic oscillations occur when a saddle-type periodic solution exists. As a consequence, transient periodic oscillations can be robust and observable. Implications of our findings to the dynamics of CTL response to HTLV-I infections in vivo and pathogenesis of HAM/TSP are discussed.

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    ABSTRACT: Stable periodic oscillations have been shown to exist in mathematical models for the CTL response to HTLV-I infection. These periodic oscillations can be the result of mitosis of infected target CD4(+) cells, of a general form of response function, or of time delays in the CTL response. In this study, we show through a simple mathematical model that time delays in the CTL response process to HTLV-I infection can lead to the coexistence of multiple stable periodic solutions, which differ in amplitude and period, with their own basins of attraction. Our results imply that the dynamic interactions between the CTL immune response and HTLV-I infection are very complex, and that multi-stability in CTL response dynamics can exist in the form of coexisting stable oscillations instead of stable equilibria. Biologically, our findings imply that different routes or initial dosages of the viral infection may lead to quantitatively and qualitatively different outcomes.
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