Modeling interleukin-2-based immunotherapy in AIDS pathogenesis

Abstract

In this paper, we sought to identify the CD4(+) T-cell dynamics in the course of HIV infection in response to continuous and intermittent intravenous courses of interleukin-2 (IL-2), the principal cytokine responsible for progression of CD4(+) T-lymphocytes from the G1 to the S phase of the cell cycle. Based on multivariate regression models, previous literature has concluded that the increase in survival of CD4(+) T-cell appears to be the critical mechanism leading to sustained CD4(+) T-cell levels in HIV-infected patients receiving intermittent IL-2 therapy. Underscored by comprehensive mathematical modeling, a major finding of the present work is related to the fact that, rather than due to any increase in survival of CD4(+) T-cells, the expressive, selective and sustained CD4(+) T-cell expansions following IL-2 administration may be related to the role of IL-2 in modulating the dynamics of Fas-dependent apoptotic pathways, such as activation-induced cell death (AICD) or HIV-specific apoptotic routes triggered by viral proteins.

Keywords: AICD; AIDS; APC; CCF; CNS; DAE; ENV; Env-CD4 cross-linking mediated apoptosis; FDC; HAART; HEV; HIV; IFN-γ; IL-12; IL-2; IU; IVST; Immune system; Immunotherapy; International Unit; LT; MHC; MIU; PB; PCD; PCR; PSVE; T-lymphocyte; TAT; Tat-induced apoptosis; VTC; acquired immunodeficiency syndrome; activation-induced cell death; antigen presenting cells; cell–cell fusion; central nervous system compartment; differential-algebraic equations; follicular dendritic cells; high endothelial venules; highly active antiretroviral therapy; human immunodeficiency virus; interferon γ; interleukin-12; interleukin-2; intracellular viral stock transference; lymphoid tissue compartment; major histocompatibility complex; million International Units; passive cell death; peripheral blood compartment; polarized secretion of viral envelopes; polymerase chain reaction; virus-to-cell.